Cytomegalovirus (CMV) remains the most important infection in the immunocompromized host even in the era of effective therapy. CMV is usually acquired early in life and can be transmitted by contact with infected body fluids. In the immunocompetent population, primary infection is almost always of little clinical consequence. However, CMV infection in immunocompromized patients, especially those naive to CMV exposure, can cause tissue invasive disease, severe symptoms and/or death. However, beyond these direct effects, increasing in vitro evidence is accumulating that suggests CMV has many other effects on the host's immune response which may explain some of the detrimental consequences for the immunosuppressed patient, and may also be partially responsible for a variety of conditions in immunocompetent individuals. In its latent state, CMV employs several mechanisms to evade detection by the host's immune system. The virus also employs other methods to take advantage of activation of the immune system and replicate in sites of inflammation. This review focuses on the immunosuppressive and inflammatory mechanisms that have been attributed to CMV and will relate them to some of the clinical sequellae that have been associated with the indirect effects of CMV infection.