Human cytomegalovirus infection is widespread, reaching over 60% of the population worldwide. Transmission occurs by direct contact with infected bodily secretions. This virus encodes many more gene products than other herpesviruses, and these contribute to both replication and pathogenesis. A majority of viral genes encode functions that modulate the host immune response and contribute to persistent infection. Although virus is generally acquired without significant disease, cytomegalovirus is a medically important opportunistic pathogen. In the developing fetus, transplacental transmission leads to neurological disease. In immunocompromised individuals, a number of organ-specific diseases may arise from acute or chronic infection. A number of antiviral drugs are available to treat this virus. Although vaccines would be useful in a number of settings, none are currently proven or available.