: Owing to more effective and less toxic antiretroviral therapy (ART), people living with HIV (PLWH) live longer, a phenomenon expected to grow in the next decades. With advancing age, effectively treated PLWH experience not only a heightened risk for non-infective comorbidities and multimorbidity, but also for geriatric syndromes and frailty. In addition, older adults living with HIV (OALWH) have a higher prevalence of so-called iatrogenic triad described as polypharmacy (PP), potentially inappropriate medication use, and drug-drug interactions. : This review will focus the management of ART in OALWH. We will discuss iatrogenic triad and best way to address PP. Special focus will be given to pharmacokinetic and pharmacodynamic aspects of ART in the elderly, evaluation of ART toxicities, and specific ART strategies commonly used in this population. : Research should be focused on recruiting more OALWH, frail individuals in particular, into the clinical trials and specific geriatric outcome need to be considered together with traditional viroimmunological outcomes.