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This article discusses the impact of depression on work productivity and the potential for improved work performance associated with effective treatment. We undertook a review of the literature by means of a computer search using the following key terms: cost of illness, work loss, sickness absence, productivity, performance, and disability. Published works were considered in four categories: (1) naturalistic cross-sectional studies that found greater self-reported work impairment among depressed workers; (2) naturalistic longitudinal studies that found a synchrony of change between depression and work impairment; (3) uncontrolled treatment studies that found reduced work impairment with successful treatment; and (4) controlled trials that usually, but not always, found greater reduction in work impairment among treated patients. Observational data suggest that productivity gains following effective depression treatment could far exceed direct treatment costs. Randomized effectiveness trials are needed before we can conclude definitively that depression treatment results in productivity improvements sufficient to offset direct treatment costs.