The evidence from research studies linking depression to excess risk for coronary heart disease (CHD) is strong and consistent. Depression is a risk factor for new cardiovascular events in individuals initially free of CHD, as well as for recurrent events and mortality among cardiac patients. The risk is not only limited to individuals who meet the criteria for a clinical diagnosis of major depression. Increasing levels of depressive symptoms, even in the absence of a major depressive episode, also carry higher CHD risk. What is less established, however, is the mechanism (or mechanisms) responsible for the effect of depression on CHD risk. Depression might increase CHD incidence by promoting or worsening coronary atherosclerosis (through effects on lipid profile, platelets and inflammatory factors), directly inducing cardiac ischemia, increasing the risk for cardiac arrhythmias and sudden death, and inducing unhealthy behaviors (cigarette smoking, decreased adherence to medications and other lifestyle factors). Depression is common in the U.S. and its prevalence is rising. It is important that individuals with depression are promptly identified and treated. This is likely to result in a reduction of CHD and related disability as well as health care costs among Americans.