Screening for depression has been so widely advocated that the burden of proof has shifted to skeptics who argue against it. Yet only recently has sufficient evidence accrued to judge dispassionately the advantages and disadvantages of screening. Here we discuss the evidence for specific tools and specific strategies in improving the outcome of depression screening in primary care. In 1978, the Institute of Medicine defined primary care as ‘‘care that is accessible, comprehensive, coordinated, continuous, and accountable.’’ While the definition has evolved over time,2 these fundamental characteristics are still valid today. Included in the primary care mission is to serve as the first line for detection and either treatment or referral of common mental disorders, including depression. The inclusion of first-line mental health services as a component of primary care distinguishes primary care (including outpatient clinics in managed care organizations, community hospitals, Veterans Administration hospitals, teaching institutions, and other medical centers) from care in more specialized clinical settings. The comprehensiveness of primary care and the obligation of its providers for first-line care make it a logical and appropriate venue for mental health screening. Complicating the issue, however, are the time constraints on primary care providers. Although the amount of time spent per patient visit is about 20 minutes in the United States, the recommended services that should be provided in that short period of time are daunting. It is therefore imperative that these recommended services—in particular preventive health services— be provided in the most efficient manner possible. Services that cannot be provided efficiently and fit within the busy, fast-paced world of primary care are at risk of being omitted. This is especially true for preventive mental health services. Screening for depression is such a service; therefore, it is critical that primary care providers make use of the best and most efficient depression screening approaches possible. In this chapter, we will address issues related to screening for depression in the primary care context. We will start by briefly reviewing the epidemiology of depression as related to primary care. Next, we will provide a critical examination of the applicability to depression screening of the World Health Organization’s criteria.