Human cytomegalovirus is a large DNA virus that is well-equipped to evade both innate and adaptive host immune responses and to establish lifelong latency. It is a major opportunistic pathogen in immunocompromised hosts. Following allogeneic transplantation, immune responses are often inadequate to inhibit viral reactivation, resulting in progressive tissue damage, manifesting as overt human cytomegalovirus disease that usually presents as pneumonitis, colitis or hepatitis. Currently available antiviral pharmacotherapies are limited by toxicities if used prophylactically, and by a lack of efficacy in established human cytomegalovirus disease. Efforts have therefore focused on molecular diagnostic surveillance protocols that allow earlier intervention and the development of adoptive immunotherapeutic strategies to hasten host immune reconstitution.