The data reported herein show clearly that major depression is a commonly occurring and burdensome disorder. The high prevalence, early age of onset, and high persistence of MDD in the many different countries where epidemiologic surveys have been administered confirm the high worldwide importance of depression. Although evidence is not definitive that MDD plays a causal role in its associations with the many adverse outcomes reviewed here, there is clear evidence that depression has causal effects on a number of important mediators, making it difficult to assume anything other than that depression has strong causal effects on many dimensions of burden. These results have been used to argue for the likely cost -effectiveness of expanded depression treatment from a societal perspective. Two separate, large-scale, randomized, workplace depression treatment effectiveness trials have been carried out in the United States to evaluate the cost effectiveness of expanded treatment from an employer perspective. Both trials had positive returns on investment to employers. A substantial expansion of worksite depression care management programs has occurred in the United States subsequent to the publication of these trials. However, the proportion of people with depression who receive treatment remains low in the United States and even lower in other parts of the world. A recent US study found that only about half of workers with MDD received treatment in the year of interview and that fewer than half of treated workers received treatment consistent with published treatment guidelines. Although the treatment rate was higher for more severe cases, even some with severe MDD often failed to receive treatment. The WMH surveys show that treatment rates are even lower in many other developed countries and consistently much lower in developing countries. Less information is available on rates of depression treatment among patients with chronic physical disorders, but available evidence suggests that expanded treatment could be of considerable value. Randomized, controlled trials are needed to expand our understanding of the effects of detection and treatment of depression among people in treatment for chronic physical disorders. In addition, controlled effectiveness trials with long-term follow-ups are needed to increase our understanding of the effects of early MDD treatment interventions on changes in life course role trajectories, role performance, and onset of secondary physical disorders.