In recent years, clinicians and epidemiologists have examined the differences between depressed patients in primary care and psychiatric settings. Although evidence to support antidepressant efficacy is largely derived from studies of major depression, many patients in primary care settings fall into "nonmajor" depression diagnostic categories. In deciding when to initiate treatment, functional change may be even more important than discrete symptom profiles. Recognizing and treating depression as a comorbid condition in patients with other medical illnesses represents an additional challenge for the primary care physician. Variations in the clinical presentation of depression based on gender, age, culture, or personality must also be considered.