People living with HIV (PLWHIV) are at high risk of anemia due to inadequate iron intake, HIV and opportunistic infections, and inflammation, and as a side effect of antiretroviral therapy. Though iron supplementation can reduce iron deficiency anemia (IDA) in the general population, its role in anemia and in the health of PLWHIV is unclear due to concerns that iron supplementation may increase HIV replication and risk of opportunistic infections. We systematically reviewed the evidence on indicators of iron status, iron intake, and clinical outcomes among adults and children with HIV. The evidence suggests that anemia is associated with an increased risk of all-cause mortality and incident tuberculosis among HIV-infected individuals, regardless of anemia type, and the magnitude of the risk is greater with more severe anemia. High serum ferritin is associated with adverse clinical outcomes, although it is unclear if this is due to high iron or inflammation from disease progression. One large observational study found an increased risk of all-cause mortality among HIV-infected adults if they received iron supplementation. Published randomized controlled trials of iron supplementation among PLWHIV tend to have small sample sizes and have been inconclusive in terms of effectiveness and safety. Large randomized trials exploring approaches to safely and effectively provide iron supplementation to PLWHIV are warranted.