In the context of solid organ transplantation, the exact interactions between the innate and adaptive alloimmune response have not yet been fully explored. In this transplant setting, natural killer (NK) cells have emerged as a particular focus of interest because of their ability to distinguish allogeneic major histocompatibility complex (MHC) antigens and their potent cytolytic activity. Based on this observation and its potential clinical relevance, NK cells have recently been shown to participate in the immune response in both acute and chronic rejection of solid organ allografts. Numerous experimental and clinical studies demonstrate that NK cells determine transplant survival by rejecting an allograft not directly but indirectly by providing bystander effects. In addition, NK cells are influenced by immunosuppressive therapies such as calcineurin inhibitors or steroids. As NK and natural killer T (NKT) cells have also been shown to play a profound role in allograft tolerance induction, this review summarizes the major findings to highlight the functional role of these lymphocyte subsets, which may constitute an underestimated mechanism affecting graft outcome in solid organ transplantation.