Cytomegalovirus (CMV) is the most common viral infection affecting the posttransplantation course of organ recipients. However, CMV involvement of the prostate even in immunocompromised hosts is rare. We describe the first case in the heart transplant literature of a 59-year-old heart recipient with CMV prostatitis. An elevated PSA prompted a prostate biopsy revealing an adenocarinoma, chronic prostatitis as well as viral cytopathic effect consistent with CMV infection. CMV PCR in the blood was negative. A few months prior, the patient developed CMV viremia and was treated initially with ganciclovir intravenously and subsequently with valganciclovir and CMV immunoglobulins. The patient did well with brachytherapy and additional anti-CMV agents. We discuss the role of CMV in the prostate and management of CMV prostatitis. Relationships between CMV, prostate cancer and heart transplantation are also outlined.