Selenium (Se) supplementation in people living with HIV (PLWH) has demonstrated benefits in terms of HIV disease progression, morbidity, and mortality. The HIV pandemic continues to be a major health priority worldwide, and the life span of PLWH increases due to the life-prolonging effects of antiretroviral therapy (ART). Subsequently, nutritional interventions become critical as adjuvant therapies. Nutritional interventions assist in the recuperation of the immune system, preventing nutritional deficiencies, and limiting oxidative stress damage, especially in an aging population on chronic ART. Se status influences HIV disease progression through its role in modulating cytokine signaling for the activation of the immune system and through its antioxidant activity. In addition, this chapter reviews other aspects of the relationship between HIV/AIDS and Se status and Se supplementation, such as associations with vaginal HIV shedding, mitochondrial damage, and HIV transmission.