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Disparities in minor histocompatibility antigens between HLA-matched organ and hematopoietic stem cell donors and recipients create the risks of graft failure and graft-versus-host disease (GvHD) respectively. A decade ago, technical advances combined with genomic information resulted in the identification of the chemical nature of the first series of minor histocompatibility antigens, facilitating their molecular typing. A new era of research had begun in exploring the role of minor histocompatibility antigens in physiological and nonphysiological settings. Here we summarize, to the best of our knowledge, human studies on the relevance of minor histocompatibility antigens in solid organ transplantation with a main focus on renal allografting.The minor histocompatibility antigen HY is associated with acute rejection, and male grafts in female recipients have reduced graft survival; both cellular and humoral responses are observed. Studies on autosomal minor histocompatibility antigens on graft rejection are less conclusive; their role in transplant tolerance, however, offers perspective.Information on the clinical relevance of minor histocompatibility antigen allo-immune responses in solid organ allografting is still scarce. The possible implications of the minor histocompatibility allo-immune responses for future clinical practice in solid organ transplantation are discussed in relation to their possible detrimental or beneficial effects on the host.