Candidate trigger antigens for alloreactive responses have been appearing continuously in the organ transplant scenario. Major histocompatibility complex class I-related chain A (MICA) is a polymorphic gene family, located near the HLA-B locus on chromosome 6, that encode a 62-kd cell surface glycoprotein. Endothelial cells, in addition to many cell lines, express MICA, whereas resting lymphocytes do not, making this polymorphic molecule a target for both cellular and humoral immune responses. Major histocompatibility complex class I-related chain A antigens are able to elicit the synthesis of alloantibodies in transplant recipients. These antibodies have been found in association with irreversible allograft rejection, an increased frequency of acute rejection episodes, and a significantly lower deceased donor graft survival, as well as in the eluates from rejected grafts. This review summarizes currently available information on MICA in the transplant setting. Undoubtedly, the questions that have surfaced surpass in excess the currently available answers.