Hematopoietic stem cell transplantation (HSCT) provides a unique environment in which to evaluate the role of immunogenetics of both the donor and the recipient to success of the procedure. The central role of HLA matching in HSCT has been established; however, recipients of allogeneic HSCT incur the risk of graft versus host disease (GVHD) even when the donor is a sibling who shares the major histocompatibility genes. Therefore, the perfect HLA match does not represent the optimal genetic make up. Other genetic systems operate and affect the various outcomes of HSCT, including GVHD, infections, transplant-related mortality, and overall survival. Minor histocompatibility antigens contribute to the control of GVHD as well as graft versus leukaemia reactions. In addition, genes controlling inflammatory processes, including cytokines, chemokines and their receptors, can modulate GVHD, and genes from both arms of the immune response (innate and adaptive) are strong candidates for susceptibility factors to infections in allogenic transplantation.