An increasing number of patients over 50 years of age are now living with HIV, owing to highly active antiretroviral therapy (HAART) that prolongs survival on the one hand and to late diagnosis of patients living with occult HIV infection on the other hand. Most studies have shown that compared with younger patients, patients over 50 generally have a slower immunological response to HAART and experience more rapid clinical progression, despite a better virological response. Low thymic output probably plays a role in the poorer CD4 cell response in patients initiating HAART over 50 years. Management of HIV infection in older patients is particularly complex, mainly because they are more likely to have co-morbidities necessitating specific medications that may interact with antiretroviral drugs. More controlled studies of HAART efficacy and tolerability in such patients are needed to establish specific management guidelines. Information campaigns targeting older patients and their doctors are also needed to ensure timely diagnosis of HIV infection and antiretroviral treatment initiation.