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Portable air cleaners (PACs) can reduce indoor concentrations of fine particulate matter (PM2.5), although their impact can vary substantially. This review explores how PAC performance measured during an intervention can be affected by the indoor and outdoor environment, device operation, and study methodology. A literature search identified 41 randomized interventions conducted in homes (64 articles) satisfying the inclusion criteria. Reporting of key contextual factors was inconsistent between investigations, and many factors were frequently absent from discussion. Average reductions in indoor PM2.5 concentration ranged from 6.3–82.7% (effectiveness) and 1.2–54.9 μg·m–3 (absolute reduction). Neither measure was positively associated with PAC cleaning power (clean air delivery rate, CADR, or volume-normalized CADR, CADR/V). Concentration reductions were frequently lower than expected based on nominal CADR/V, suggesting that PACs operated at lower speeds than reported and/or that room dimensions underestimate the mixing volume of a space. Effectiveness was greater when windows were closed and when testing was conducted in bedrooms compared with living rooms. Absolute reductions were greater, with larger variance, as ambient PM2.5 concentrations increased. Accounting for these factors may strengthen assessments of past and future interventions and guide the implementation of PACs to reduce indoor PM2.5 concentrations and improve associated health outcomes.