HIV infection is associated with chronic immune activation that is superimposed on immunologic senescence in older adults, resulting in the acquisition of age-related diseases at younger ages. The incidence of coronary artery disease is higher among HIV-infected persons than uninfected individuals matched for age and sex. HIV infection and its treatment have been associated with premature bone loss. Lung, hepatic, and anal cancers occur at younger ages in persons with HIV infection. HIV-infected patients are living longer, and proper attention to the management of comorbidities in this population is essential. This article summarizes an IAS-USA continuing education webinar presented by Howard Libman, MD, in January 2015.