Indoor air quality (IAQ) plays a critical role in human health, yet indoor pollutants frequently accumulate despite improvements in ventilation and building design. Air cleaners are increasingly used as a complementary mitigation strategy, but their real-world effectiveness and clinical relevance remain heterogeneous. This review synthesizes evidence from 36 peer-reviewed studies to evaluate the pollutants targeted by air-cleaning technologies, their removal efficiency under realistic conditions, and their associations with respiratory, cardiovascular and other health outcomes. HEPA-based systems consistently reduce indoor particulate matter (PM), often by 20–80%, and show moderate evidence for short-term cardiopulmonary benefits, including reductions in blood pressure and inflammatory biomarkers. In contrast, evidence for gaseous pollutant removal, long-term health outcomes, cognitive effects and economic impacts remains limited, and some technologies may generate harmful byproducts such as ozone. The review also considers implications for vulnerable populations and energy-efficient buildings where ventilation may be constrained. By critically evaluating multidisciplinary evidence, this work bridges the gap between air-cleaning performance metrics and public-health relevance, supporting informed decision-making for practitioners, policymakers and building professionals.