The number of HIV patients over the age of 50 years is increasing due to increased longevity in patients treated with highly active antiretroviral therapy (HAART), in addition to new primary infections in older patients. Numerous studies have demonstrated worse HIV disease progression and mortality in older HIV patients compared with younger patients. While HAART therapy has been shown to be effective at reducing HIV-1 RNA, the immunologic benefits in older patients may be reduced compared to younger patients. Older patients are more likely to suffer comorbidities requiring concomitant medications than younger patients. Toxicities from HAART, particularly dyslipdemia, insulin resistance, and pancreatitis may also be worse in older HIV patients. Controlled trials on epidemiology, pathogenesis, and therapeutic and clinical outcomes in the elderly are needed. As the HIV-infected population ages, there is a growing need to better determine the efficacy of HAART in older patients, and to investigate factors associated with a more rapid course of HIV infection in patients over the age of 50 years.