Objective: The association between depression and cardiovascular disease has been well documented but the nature of this relationship continues to be defined. Given the accumulation of epidemiological evidence linking these diseases a number of interventional studies have been undertaken to assess the issue of whether antidepressant treatment in depressed patients with cardiovascular disease improves cardiac outcome. The objective of this paper is to review recent randomised controlled trials on this topic and to explore the implications that these may have for future research in this area. Method: This review is derived from a MEDLINE search using the search terms ‘depressive disorder’ and ‘cardiovascular diseases’. Only randomised controlled trials published in English with clearly defined methods and interventions are included here. Reference sections from the articles were used to identify additional relevant studies. Results: A small number of high quality trials were uncovered which indicated mixed results in terms of the treatment of depression in cardiovascular disease. None indicated a statistically significant difference in cardiac outcome. Conclusions: It is not possible at this time to recommend treatment for depression to reduce cardiovascular risk. However depression remains prevalent in patients with cardiovascular disease and is a treatable cause of morbidity in its own right. © 2006, International Committee of the Red Cross. All rights reserved.