Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in patients with an impaired immune system. The virus itself can cause transitory but significant immunosuppression in immunocompetent as well as immunocompromised infected individuals. Besides immunosuppression, HCMV-infected patients often develop other signs of immune dysfunction, such as autoimmune phenomena. Signs of active viral infection have also been identified in inflammatory lesions in a number of autoimmune diseases, highlighting the potential role of HCMV in the genesis or maintenance of such immunopathological phenomena. HCMV targets several cells of the immune system and subverts host immune functions to its own advantage. We present here an overview of the effects of HCMV infection on antigen-presenting cells and relate in vitro data to immunopathological findings in HCMV-infected patients. Possible mechanisms by which HCMV can induce host immunopathology will also be discussed. Copyright © 2009 John Wiley & Sons, Ltd.