The causes of morbidity and mortality for people with HIV infection have evolved substantially in the HAART era. In addition to the traditional common opportunistic disease of the pre-HAART era, increasing attention has been focused on the so-called non-AIDS events, including cardiovascular disease, renal disease, endocrinopathies, and malignancies. A key question for studying these conditions is, What is HIV-related? Evidence presented in the past several years suggests that a variety of what were previously considered non-AIDS events are indeed related to HIV. The pathogenesis of these conditions may be related to immunodeficiency, inflammation, or other causes. Co-infections remain a serious challenge to managing HIV infection, and their importance has grown as HAART has become available in the developing world. TB continues to be the most common opportunistic disease among people with HIV; the key issues in TB/HIV are prevention, co-management, and immune reconstitution disease. Serious fungal infections, particularly cryptococcosis, raise similar questions. Finally, chronic viral hepatitis is an important clinical problem for millions of patients. Co-treatment of hepatitis B in HIV-infected people is now feasible and may dramatically alter the natural history of this disease. Treatment options for hepatitis C are less effective and more toxic, underscoring the need for more research in this area.