Depression is a highly treatable disease that is more prevalent among primary care patients than hypertension. Primary care physicians must become accustomed to screening for and treating depression just as they screen for and treat hypertension. A psychiatrist should be consulted for severe cases of depression. The introduction of the serotonin selective reuptake inhibitors (SSRIs), antidepressants that are far less toxic and have a milder side effect profile than the tricyclic antidepressants (TCAs), has made it possible for depression to be treated more successfully in the primary care setting. Unlike the TCAs, the SSRIs have not been lethal in overdose. Early diagnosis and early treatment can reduce the morbidity and mortality associated with depression and can also reduce the costs associated with misdiagnosis. This article reviews the difficulties inherent in diagnosing depression in this health care setting, including somatization and the coexistence of other medical disorders. Suggestions are offered for effective screening and diagnosis, and a practical approach is given for explaining the diagnosis, which may help moderate patient denial or fear of stigma. Current pharmacotherapeutic options for treating mild-to-moderate depression are also summarized.