Cytomegalovirus (CMV), a member of the Herpes virus family, is a seemingly harmless infectious agent for healthy individuals. However, it is one of the most important opportunistic pathogens in immunosuppressed patients, particularly in organ transplant recipients. Due to its monocytotropic character, CMV exhibits an intimate relationship with the host immune system, and is therefore of great interest to immunologists. In this review, a summary is given of recent developments in our understanding of the interaction between CMV and the host immune system and guidelines are provided for the clinical management of this infection.