This review summarizes the state-of-the-art knowledge on diagnosis, pathogenesis, immune response to, clinical picture, treatment and prevention of cytomegalovirus (CMV) infection in humans. CMVs are ubiquitous betaherpesviruses that infect animals as well as humans. Primary infection with human cytomegalovirus (HCMV) is followed by persistence of the virus in a latent form. During life, the virus can reactivate, resulting in renewed shedding of the virus or development of disease. Redundant molecular mechanisms have been identified by which CMVs interfere with the host immune control, but finally, the infection is held in check by the host's immune response. As a consequence, CMV disease is restricted to the immunocompromised or immunologically immature host. HCMV is the leading cause of congenital infections, with an incidence of 1-2.4% of live births, with possible severe classic" cytomegalovirus inclusion disease" in 10% of them. Congenital CMV infection is the leading infectious cause of brain damage and hearing loss in children and also a relevant health issue to transplant recipients and human immunodeficiency virus (HIV)-infected patients. Significant progress has been made in the last few years in detecting CMV, but in the immunocompromised patients, establishing the diagnosis of CMV infection can still be problematic. The most sensitive molecular amplification methods such as polymerase chain reaction (PCR) should be used. The decision how to treat the infection depends mainly on the immune status of the host. In immunocompetent patients only symptomatic treatment is recommended, while in immunocompromised patients antiviral therapy and immunotherapy should be used. The most commonly used antivirotics are: ganciclovir, foscarnet, cidofovir, valganciclovir, valaciclovir.