Immunity mechanisms of cytomegalovirus infection control have been studied recently and have contributed to the better understanding of the pathogenesis of this disease in patients with a solid organ transplant. These studies suggest that a relationship exists between cytomegalovirus and the development of acute rejection. This relationship is more evident if the patient develops cytomegalovirus disease and if the donor is cytomegalovirus-positive and the recipient is cytomegalovirus negative. There is also evidence that the association is probable if there is coinfection with cytomegalovirus and other herpesviruses (human herpesvirus 7). Over the past 30 years, many attempts have been made to design vaccines able to prevent cytomegalovirus infection and disease; however, few vaccines progressed to clinical studies and none have been licensed yet. The purpose of this review is to provide a critical analysis of the most recent evidences from the medical literature with respect to the pathogenesis of cytomegalovirus infection and its association with acute and chronic rejection, as well as the possible implications that the development of future vaccines could have in the prevention of cytomegalovirus disease and acute or chronic rejection.