Older adults make up an ever-growing proportion of human immunodeficiency virus (HIV) cases in the United States, with approximately 25% of infections occurring in adults over the age of 50 years. Although there is a preliminary body of literature addressing the socioeconomic and prognostic issues of HIV infection in older adults, very little rigorous scientific research has looked at the significant clinical issues relevant to this growing population. Treatment of older adults is complicated by an increased prevalence of medical comorbidities, but little is known about the effects of complicated medication regimens in this group, as they are routinely excluded from clinical trials of newer HIV medications. The delay in diagnosis and treatment of HIV in older adults has led to poorer outcomes, including lower baseline CD4 counts, decreased time to acquired immune deficiency syndrome diagnosis, and increased mortality. Despite these facts, there is mounting evidence that timely diagnosis and treatment of HIV in older adults leads to improved outcomes, similar to younger patients. This review evaluates the literature focusing on HIV and older adults.