PURPOSE OF REVIEW: This review will discuss statin therapy for prevention of cardiovascular disease (CVD) among people with HIV (PWH) in the context of balancing prevention and treatment of chronic diseases with challenges related to polypharmacy. RECENT FINDINGS: Aging PWH confront an increased risk of chronic diseases, resulting in the need for prevention and treatment of comorbidities in addition to antiretroviral therapy (ART). Paradigm-shifting data from the REPRIEVE trial demonstrated a reduction in CVD events with statin therapy among PWH at low to moderate CVD risk, prompting the Department of Health and Human Services (HHS) to recommend statin therapy for primary prevention of CVD in people with HIV aged 40-75 years. Statins should be initiated according to guideline recommendations for CVD prevention, and discussion of statin initiation should include consideration of concurrent medications and the potential effects of polypharmacy. SUMMARY: Statins should be initiated for primary prevention of CVD in people with HIV age 40-75 years. The effects of polypharmacy should be considered in all aging PWH. Prevention and treatment of chronic diseases among PWH is important to reduce morbidity and mortality and promote healthy aging.