This review considers evidence for the efficacy of pharmacotherapy among primary care patients with depressive disorders and reviews knowledge regarding the effectiveness of current practice. Strong evidence supports the efficacy of antidepressant pharmacotherapy for primary care patients with major depression and dysthymia with some evidence for pharmacotherapy of less severe depression. In general, available antidepressants appear equal in both efficacy and effectiveness. Treatment selection for any individual patient remains largely empirical, with few clinical characteristics predicting better or worse response to specific treatments. Strong evidence supports continuation treatment (i.e., at least six months of pharmacotherapy) for all patients and maintenance treatment (i.e., at least 24 months of pharmacotherapy) for those with chronic or recurrent depression. Unfortunately, few patients in primary care or specialty practice receive recommended levels of pharmacotherapy or recommended frequency of follow-up care. A number of recent studies have evaluated strategies to improve the quality of antidepressant treatment in primary care. Educational programs (including academic detailing and continuous quality improvement) have had little impact on patient outcomes. Key elements of effective care improvement programs include specific, evidence-based treatment protocols, organized patient education and active follow-up care.