Antiretroviral therapy has revolutionized the care of people with human immunodeficiency virus (HIV) by reducing morbidity and mortality from acquired immunodeficiency syndrome–related conditions. Despite longer life expectancy, however, HIV-infected individuals continue to have a higher risk of death compared with the general population. This has been attributed to the increasing incidence of noncommunicable diseases, in particular, atherosclerotic cardiovascular diseases. This is driven, in part, by the emergence of metabolic disorders, particularly dyslipidemia, insulin resistance, and lipodystrophy, in those on antiretroviral therapy. The pathogenesis of these metabolic derangements is complex and multifactorial, and could be a consequence of an interplay between traditional age-related risk factors, HIV infection, antiretroviral therapy effects, and the inflammatory state and immune activation in this population. Understanding the contributions of each of these factors could not just impact the current management of these individuals and help mitigate the risk for premature cardiovascular disease, but also shape the future direction of research in HIV.