Unipolar major depression ranks among the leading contributors to the global burden of disease. Although established risk factors for depression include a variety of individual-level characteristics, neighborhood etiologic factors have been relatively understudied, with several such attributes (neighborhood socioeconomic status, physical conditions, services/amenities, social capital, social disorder) possessing plausible linkages to depression. Using the PubMed database (1966-2008) and the Social Sciences Citation Index database (1956-2008), the author undertook a systematic review of the published literature on the associations between these characteristics and depression in adults. Across studies, the evidence generally supports harmful effects of social disorder and, to a lesser extent, suggests protective effects for neighborhood socioeconomic status. Few investigations have explored the relations for neighborhood physical conditions, services/amenities, and social capital, and less consistently point to salutary effects. The unsupportive findings may be attributed to the lack of representative studies within and across societies or to methodological gaps, including lack of control for other neighborhood/non-neighborhood exposures and lack of implementation of more rigorous methodological approaches. Establishing mediating pathways and effect-modifying factors will vitally advance understanding of neighborhood effects on depression. Overall, addressing these gaps will help to identify what specific neighborhood features matter for depression, how, and for whom, and will contribute to curtailing the burden of disease associated with this major disorder.