The median age of HIV-infected patients is increasing all over the world. Age has a significant impact on some aspects of HIV-infection when compared to younger patients. Diagnostic delay and late presentation are more frequent in older patients because some of the initial symptoms are masked by age and because older people are not considered to be a risk group for HIV infection. Despite the clinical, immunological, and virologic benefits of HAART, most studies suggest that older patients have a poorer immunological and clinical response to HAART than younger patients, despite a similar virologic response. Other problems include the frequent presence of comorbid conditions and medications that can affect the efficacy and safety of HAART as well as its pharmacokinetics and pharmacodynamics. Because no guidelines recommend a specific HAART regimen for older people, specific clinical trials and pharmacological studies should be designed to optimize HAART in these patients.