BACKGROUND: High levels of public spending, rising costs of treatments and scarcity of mental health resources have intensified the need for information on the cost-effectiveness of interventions for depression. There have been few reviews that consider the cost-effectiveness of all treatments for depression together. METHODS: Systematic review of published economic evaluations of interventions for depression to identify where evidence of cost-effectiveness exists and where ambiguity remains. RESULTS: Fifty-eight papers met the criteria and were included in the review. The quality of the evaluations varied greatly. Evidence establishing the cost-effectiveness of interventions for depression is accumulating; selective serotonin reuptake inhibitors (SSRI) and the newer antidepressants venlafaxine, mirtazepine and nefazodone appear cost-effective compared with older drugs. Despite the availability of high quality economic evaluations of psychological therapies compared to usual care, there is limited evidence of their cost-effectiveness particularly when compared directly to pharmacotherapies. Changes to health systems have been found to be cost-effective in some patient groups, but there is no evidence that screening in primary care populations is a cost-effective strategy. LIMITATIONS: Vastly different interventions, outcome measures and cost perspectives meant a meta-analysis of costs and effects was not considered possible. CONCLUSIONS: On the basis of available evidence, it is not possible to identify the most cost-effective strategy for alleviating the symptoms of depression, although the SSRIs and newer antidepressants consistently appear more cost-effective than tricyclic antidepressants in many patient groups. Better quality economic evidence is needed.