Affective disorders impose a substantial individual and societal burden. Despite availability of efficacious treatments and practice guidelines, unmet need remains high. To reduce unmet need and the burden of affective disorders, information is needed on the distribution of burden across stakeholders, on barriers to reducing burden, and on interventions that effectively reduce burden at the levels of practice, community, and policy. This article provides the report of the Working Group on Overcoming Barriers to Reducing the Burden of Affective Disorders, for the National Institute of Mental Health Strategic Plan on Mood Disorders. We review the literature, identify key gaps, and recommend new research to guide national efforts to reduce the burden of affective disorders.