Cytomegalovirus (CMV) infection is a frequent source of morbidity after heart transplantation. Risk factors for the development of CMV infection include the use of antilymphocyte preparations in the postoperative phase or as antirejection therapy, and seronegative patients who receive a heart from a seropositive donor. Clinical spectrum varies from a mild illness with low-grade fever and leukopenia, to a severe disease with organ manifestations. CMV interferes in the immune system, and may trigger cellular rejection episodes, having a possible role accelerating graft coronary vasculopathy. Thus, an aggressive and early diagnostic approach to the infection is mandatory. Quantitative monitoring of antibody titers, cultures and CMV antigenemia may be helpful in the clinical diagnosis. Cytomegalovirus prophylaxis strategies in high-risk patients remain controversial. Currently, ganciclovir is the most safe and effective agent for the treatment of CMV infection. A better knowledge of the pathogenic mechanism of CMV infection will probably help the development of new diagnosis technology and more effective prophylactic and treatment strategies.