The economic burden of depression includes direct costs of treatment, as well as absenteeism and reduced productivity. In this study, we consider the costs and benefits of an intervention to assess and treat depressive symptoms in long-term disability claimants with nonpsychiatric medical illnesses. Cost-benefit simulations were conducted using data from a study sample of long-term disability claimants (N = 1229) and estimates of both the costs of treatment of depressive symptoms and the savings in claims payments for those who return to work as a result of treatment. We show that the savings that stem from returning a very few claimants to work can offset the assumed cost of a comprehensive program for the assessment of depressive symptoms in all claimants and intensive treatment of those with depressive symptoms. The economic and public health benefits both point toward the value of such an intervention for disability claimants.