Cost-of-illness research has shown that depression is associated with an enormous economic burden, in the order of tens of billions of dollars each year in the US alone. The largest component of this economic burden derives from lost work productivity due to depression. A large body of literature indicates that the causes of the economic burden of depression, including impaired work performance, would respond both to improvement in depressive symptomatology and to standard treatments for depression. Despite this, the economic burden of depression persists, partly because of the widespread underuse and poor quality use of otherwise efficacious and tolerable depression treatments. Recent effectiveness studies conducted in primary care have shown that a variety of models, which enhance care of depression through aggressive outreach and improved quality of treatments, are highly effective in clinical terms and in some cases on work performance outcomes as well. Economic analyses accompanying these effectiveness studies have also shown that these quality improvement interventions are cost efficient. Unfortunately, widespread uptake of these enhanced treatment programmes for depression has not occurred in primary care due to barriers at the level of primary care physicians, healthcare systems, and purchasers of healthcare. Further research is needed to overcome these barriers to providing high-quality care for depression and to ultimately reduce the enormous adverse economic impact of depression disorders.