Anthony Peter Monaco was a legendary and pioneering transplant surgeon and basic scientist at Beth Israel Deaconess Medical Center and the distinguished Peter Medawar professor of surgery at Harvard Medical School. He was also president of the American Society of Transplant Surgeons (from 1985 to 1986) and of the Transplantation Society (International) (from 1986 to 1988). He contributed to major advances in clinical transplantation, organ donation and procurement, and basic transplant immunology for over five decades. He was born on 12 March 1932, the son of Donato Monaco, who was originally from Italy, and Rose Monaco née Consalvi, and grew up in Philadelphia. He graduated from the University of Pennsylvania in 1952 and from Harvard Medical School in 1956, where he was a national scholar and received the Henry Asbury Christian award. Following medical school, he was an intern and resident at the Massachusetts General Hospital (MGH) and then a research fellow in immunology and the American Cancer Society clinical fellow at Harvard Medical School (from 1956 to 1963). In 1963 he took a position at MGH as an assistant in surgery and instructor of surgery at Harvard Medical School. In 1967 Monaco became an associate visiting surgeon, fifth (Harvard) surgical service, Boston City Hospital, and chief of the transplantation division, Sears surgical research laboratory of Harvard Medical School, Boston City Hospital. He moved to the New England Deaconess Hospital in 1974, where he served as chief of the division of organ transplantation from 1975 to 1995 and, after the merger of the Beth Israel and New England Deaconess hospitals, served as chief of the division of organ transplantation at Beth Israel Deaconess Medical Center (BIDMC) from 1997 to 2001. He also served as president of the medical staff and member of the board of trustees of the New England Deaconess Hospital. During this time, he also established the kidney transplant program at Rhode Island Hospital (RIH) and was also director of transplant services at RIH from 1997 to 2009. Monaco served as the chairman of the New England Organ Bank (NEOB), the first organ procurement organisation in the United States, from 1973 to 1976 and from 1981 to 1985. This was in recognition of his numerous contributions to the pioneering efforts to organise, standardise and expand deceased donor organ donation in New England as a founding trustee of the NEOB. Monaco became an assistant professor of surgery at Harvard Medical School in 1967, associate professor of surgery in 1969 and professor of surgery in 1977. In 1995 he was appointed the Peter Medawar professor of surgery. He was also a member of the board of academic advisers, Harvard Medical School (from 1974 to 1983). Monaco was a busy clinician performing kidney transplants, donor nephrectomies, dialysis access and general surgical procedures in transplant patients throughout his career. He was recognised for his expert technical ability, superior clinical knowledge and judgment, and ability and success in teaching and mentoring several generations of medical students, surgical residents, transplant fellows, faculty and research investigators. He had an abiding interest in and dedication to studying clinical problems in the laboratory with the intention of applying them clinically. He was admired and beloved by all his students, colleagues and staff. Many of his former students are current leaders in clinical transplantation and transplant immunology. He retired from clinical surgery in 2007 but continued to be an active member of the transplant institute at BIDMC until his death. It is impossible to adequately summarise in a short paragraph Monaco’s many original contributions in experimental and clinical transplantation that were focused in three primary areas. First, he did innovative work demonstrating the lymphocyte depleting and immunosuppressive properties of extremely potent polyclonal antilymphocyte antibodies (ALS) for experimental and clinical use. Studies by Monaco and his colleagues proved the effectiveness of ALS in prolonging large animal vascularised solid organ allograft survival. They were critically important for two reasons; they provided a scientific basis to develop a human ALS for clinical use and they introduced the concept of biological induction therapy – that ALS treatment might enhance the effectiveness of immunosuppressive drugs and/or decrease the dose required for maintenance immunosuppression. Monaco and his colleagues were among the first investigators to examine the effects of anti-human ALS in man. His sequential studies in mice, dogs and humans provided a solid experimental basis and strong impetus to develop polyclonal ALS for use in human clinical transplantation. Second, he demonstrated the unique tolerogenicity of donor bone marrow to induce specific recipient hyporesponsiveness. Monaco noted that mice given ALS, particularly after adult thymectomy, exhibited tissue and peripheral lymphopenia and associated immune incompetence similar to that seen in neonatal animals (mice) in whom Medawar and colleagues had induced immunological tolerance to skin allografts by intravenous donor lymphoid cell injections. These studies were the first to demonstrate that donor bone marrow specifically enhanced survival of vascularised whole organ allografts in recipients treated with depleting antibodies – clearly foreshadowing the tolerance strategies used in clinical tolerance protocols. Third, Monaco and his colleagues developed several new tolerance strategies using depleting polyclonal antilymphocyte antibodies, donor bone marrow and clinical immunosuppression that were effective in large and small animal models and were based on their pioneering laboratory work including the identification of a tolerogenic fraction of active bone marrow cells consistent with that of a natural suppression or regulatory cell. He performed the first kidney/bone marrow transplant in a patient in the mid-1970s. These areas of research continue to have substantial impact on experimental and clinical transplantation. Polyclonal antilymphocyte antibodies are regularly used in transplantation biology studies requiring reliable methodology to induce transient immune suppression. Some 50 years after their immunosuppressive effect in humans was identified, polyclonal antibodies are the most commonly used clinical biological immunosuppressive agent for induction, to achieve steroid sparing, to counteract high immunological risk and to facilitate immunosuppressive drug minimisation strategies. The unique tolerogenic ability of donor bone marrow to induce permanent tolerance in association with transient chimerism in protocols involving lymphocyte depletion and short-term clinical immunosuppression has been confirmed clinically. Monaco was the editor of *Transplantation* from 1969 to 2001 and served on the editorial boards of several other academic journals including *Transplantation Proceedings* and *Transplantation Science*. He received many awards throughout his illustrious career including the Lederle Medical Faculty award of Harvard University (in 1968); the Sir Peter Medawar prize of the Transplantation Society (in 1998), the Felix Rapaport prize of Baskent University in Turkey (in 2000) and the Roche Pioneer award of the American Society of Transplant Surgeons (in 2002). He became an honorary fellow of the Royal College of Surgeons of England in 1996. Monaco, however, was more proud of his family than any of his many clinical and research accomplishments. His wife of 58 years, Mary Louise ‘Mary Lou’ (née Oudens) died in 2018. He treasured time at the family’s Vermont ski home, where he and Mary Lou skied into their eighties, and welcomed family and friends for decades. He always valued his time with his children and grandchildren above all else, never missing their ski dates, little league or soccer games, or other school and extracurricular activities. He always saw the good in everyone and encouraged his children and grandchildren to do the same. He never expected his children and grandchildren to follow in his footsteps, but to find a profession or vocation that they loved and would complete their lives and make the world a better, safer, happier place. Monaco died on 22 August 2022 at the age of 90 in Boston, Massachusetts and was survived by his sons Peter, Mark and Christopher, his daughter Lisa and four grandchildren. He is remembered by those who worked with him over the years as a superb surgeon, thoughtful scientific innovator, and a kind and collaborative leader and mentor in the field of transplantation. He was a friend and colleague to many. His legacy will live on through the patients he cared for, the clinicians and scientists he trained, the scientific advances that continue to have an impact on patient care, and through the scientific work that continues because of the foundations that his work provided.