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Aim of this report is to review the epidemiological and clinical features of HCMV infection in the adult. In all geographical areas high diffusion of HCMV infection involving all socioeconomic groups is observed; significant most elevated seroprevalence in North African and Asian ethnic groups is compared to Western populations is pointed out; besides, HCMV is absolutely the virus most frequently transmitted in the perinatal period. In the immunocompetent host, the HCMV infection is symptomless in the great majority of cases; in the symptomatic cases it shows the clinical features of a self-limited mononucleosis-like syndrome. In the immunocompromised patients, either in subjects infected with HIV or in onco-hematologic patients or recipients of solid organ or bone marrow transplants patients, HCMV infection leads to serious illness. The most frequent clinical pictures are: pneumonia, retinitis, hepatitis, polyradiculopathy, encephalitis, gastrointestinal tract disease, adrenal involvement; cases of myocarditis, pancreatitis, genitourinary localizations are less frequent. The clinical pictures are different in the different clinical groups: retinitis, in subjects with HIV infection and pneumonia in recipients of transplants, are respectively the main clinical manifestations; the mechanisms of such differences are not clearly defined. A to the diagnosis, the serological tests (evidence of IgM activity, IgG avidity) are useful in the immunocompetent host; whereas, in the immunocompromised host cytological detection (demonstration of typical cytological aspects and positive immunohistology for HCMV antigens) and/or virological detection (isolation of virus or evidence of viral antigens or viral DNA) are needed. The most used therapeutical choices are ganciclovir, foscarnet and cidofovir; these three drugs have similar antiviral effectiveness, but they show different outlines of toxicity and praticality of use.