Major depression may be the most common medical or psychiatric disorder seen in primary medical care clinics, occurring in approximately 6 to 10 percent of the clinic populations. Despite this high prevalence rate, patients with depression often go undiagnosed or are misdiagnosed. The evidence suggests a multifactorial etiology for this problem. Many patients with depression selectively focus on the somatic components of their depressive syndrome and minimize or even deny affective and cognitive symptoms. Depression and medical disorders also often occur concomitantly with depression causing amplification of somatic complaints. Due to the unidimensional focus on the biomedical model many physicians only evaluate and treat the physical illness and do not diagnose the depression. This often leads to aggressive medical testing and treatment that carries the risk of iatrogenic injury (polysurgery, multiple tests and procedures, prescription of opiates and benzodiazepines). Several interventions are suggested to improve the diagnostic acumen of primary care physicians.