Depression has a profound impact on patient health, individual and family quality of life, activities of daily living, and daily functioning, as well as on healthcare providers, payers, and employers. Persons with depression tend to have multiple comorbidities that compound the negative effects and increase costs. The economic burden of the disease is significant, with direct medical costs estimated at $3.5 million per 1000 plan members with depression. Depression is significantly underdiagnosed and undertreated, particularly in primary care where the majority of patients with depression seek care. Effective strategies to achieve remission have been identified and have proven effective in clinical trials. Early detection, intervention, and appropriate treatment can promote remission, prevent relapse, and reduce the emotional and financial burden of the disease.