This article summarizes a comprehensive, systems-oriented framework designed to improve the use of a wide variety of evidence sources to address population-wide obesity problems. The L.E.A.D. framework (for "Locate" the evidence, "Evaluate" the evidence, "Assemble" the evidence, and inform "Decisions"), developed by an expert consensus committee convened by the Institute of Medicine, is broadly applicable to complex, community-wide health problems. The article explains how to use the framework, presenting an evidence typology that helps specify relevant research questions and includes examples of how particular research methodologies and sources of evidence relate to questions that stem from decision-maker needs. The utility of a range of quantitative, qualitative, and mixed method designs and data sources for assembling a broad and credible evidence base is discussed, with a call for ongoing "evidence generation" to fill information gaps using the recommended systems perspective.