Depressive illness places an enormous economic burden on health services, the community and the individual patient. It is a serious medical disorder associated with high levels of social and physical disability. Antidepressant drug therapy can produce significant improvement in the majority of patients. However, despite its high prevalence depressive illness is frequently undetected, misdiagnosed or inappropriately treated. The selection of a cost-effective antidepressant requires a broad evaluation of the risks, costs and benefits. A choice should not be made on prescription drug costs alone but on the basis of the overall value a treatment option offers in the management of illness. Benefits, such as improved treatment compliance, reduced toxicity in overdose, long-term safety and efficacy in the prevention of relapse and recurrence of depression, improved patient quality of life and decreased accident liability all have cost implications which must be considered when determining the relative cost of medication.