Cytomegalovirus (CMV), the largest of the herpesviruses, causes a wide range of clinical syndromes, from asymptomatic infection to severe disease in immunocompromised hosts. Laboratory methods for diagnosis include molecular testing, antigenemia, culture, serology, and histopathology. Treatment of CMV infection and disease is indicated in selected immunocompromised hosts, and preventive approaches are indicated in high-risk groups. This chapter reviews the epidemiology, clinical aspects, and the laboratory diagnosis and management of CMV in immunocompromised hosts.