BACKGROUND: An estimated 2.4 billion people still lack access to improved sanitation and 946 million still practice open defecation. The World Health Organization (WHO) commissioned this review to assess the impact of sanitation on coverage and use, as part of its effort to develop a set of guidelines on sanitation and health. METHODS AND FINDINGS: We systematically reviewed the literature and used meta-analysis to quantitatively characterize how different sanitation interventions impact latrine coverage and use. We also assessed both qualitative and quantitative studies to understand how different structural and design characteristics of sanitation are associated with individual latrine use. A total of 64 studies met our eligibility criteria. Of 27 intervention studies that reported on household latrine coverage and provided a point estimate with confidence interval, the average increase in coverage was 14% (95% CI: 10%, 19%). The intervention types with the largest absolute increases in coverage included the Indian government's "Total Sanitation Campaign" (27%; 95% CI: 14%, 39%), latrine subsidy/provision interventions (16%; 95% CI: 8%, 24%), latrine subsidy/provision interventions that also incorporated education components (17%; 95% CI: -5%, 38%), sewerage interventions (14%; 95% CI: 1%, 28%), sanitation education interventions (14%; 95% CI: 3%, 26%), and community-led total sanitation interventions (12%; 95% CI: -2%, 27%). Of 10 intervention studies that reported on household latrine use, the average increase was 13% (95% CI: 4%, 21%). The sanitation interventions and contexts in which they were implemented varied, leading to high heterogeneity across studies. We found 24 studies that examined the association between structural and design characteristics of sanitation facilities and facility use. These studies reported that better maintenance, accessibility, privacy, facility type, cleanliness, newer latrines, and better hygiene access were all frequently associated with higher use, whereas poorer sanitation conditions were associated with lower use. CONCLUSIONS: Our results indicate that most sanitation interventions only had a modest impact on increasing latrine coverage and use. A further understanding of how different sanitation characteristics and sanitation interventions impact coverage and use is essential in order to more effectively attain sanitation access for all, eliminate open defecation, and ultimately improve health.