The population of patients with HIV infection achieving viral suppression on combination antiretroviral therapy is growing, aging, and experiencing a widening spectrum of non-AIDS diseases. Concurrently, AIDS-defining conditions are becoming less common and are variably associated with outcome. Nonetheless, the spectrum of disease experienced by those aging with HIV remains strongly influenced by HIV, its treatment, and the behaviors, conditions, and demographics associated with HIV infection. Our focus must shift from a narrow interest in CD4 counts, HIV-RNA, and AIDS-defining illnesses to determining the optimal management of HIV infection as a complex chronic disease in which the causes of morbidity and mortality are multiple and overlapping. We need a new paradigm of care with which to maximize functional status, minimize frailty, and prolong life expectancy. A composite index that summarizes a patient's risk of morbidity and mortality could facilitate this work and help chart its progress.