Studies in patients recovering from myocardial infarction, episodes of unstable angina, coronary bypass surgery and coronary angioplasty, show that between 12 and 20% of hospitalized cardiac patients meet psychiatric criteria for current major depression. A similar percentage report elevated levels of depressive symptoms on paper and pencil self-report measures. These rates of depression are about three times higher than in the general community. On a practical basis this means that about one in three hospitalized CAD patients has some degree of depression. Despite its high prevalence in patients with CAD, depression is not a normal reaction to cardiac disease. Both major depression and elevated depressive symptoms are associated with at least a doubling in risk of subsequent cardiac events, even when standard cardiac risk factors, including left ventricular ejection fraction and number of blocked coronary arteries, are taken into account. In fact, several large, longitudinal community-based studies show that depression precedes the development of clinically evident CAD by many years. There is substantial evidence that depression is a potentially modifiable cardiac risk factor of as much importance as diabetes or lack of exercise. Although the precise mechanisms explaining the link between depression and CAD remain unknown, there is evidence that changes in autonomic regulation, sub-chronic inflammation, endothelial dysfunction, enhanced platelet responsiveness and reduced omega-3 free fatty acid levels may all be involved. Intriguingly, the mechanisms that have been hypothesized to explain the link between depression and CAD prognosis are the same as those suggested to explain the favorable impact of omega-3 supplements in CAD patients. Additional clinical trials to assess the impact of omega-3 supplements on depression are clearly warranted both in CAD patients and in individuals free of heart disease.