Metabolic changes characteristically observed with HIV infection include low total and high-density lipoprotein (HDL) cholesterol and elevated triglycerides. Initiation of antiretroviral therapy (ART) may increase HDL but may also elevate low-density lipoprotein, very-low-density lipoprotein, and triglycerides as well as contribute to insulin resistance and morphologic changes (ie, visceral, breast, local fat accumulation, subcutaneous fat loss). This may result in a risk of cardiovascular disease substantially higher than among age- and sex-matched individuals in the general population. Cardiovascular risk calculators, such as the Framingham calculators, may underestimate risk in the setting of HIV and therapy. The degree of cardiovascular and metabolic risk can be managed with diet and lifestyle interventions and lipid-lowering pharmacotherapy, as in the general population. In addition, drug selection and treatment switching to agents with less impact on metabolic effects can reduce metabolic risk in HIV-positive individuals receiving ART.