The association of depression with insulin resistance (IR) and athersclerotic vascular diseases has been well documented. This review examines the relevance of IR as a link between depressive disorder and atherosclerotic vascular diseases. Relevant articles collected from Medline database over the period of 1966-2001 were reviewed. Studies have shown that IR is a state-dependent abnormality in depression and depression increases the risk of vascular morbidity and mortality. Given that IR is a central component of cardiovascular risk factors, depression-related IR might play a role in the development and progression of coronary and cerebral atherosclerosis in chronic-resistant depression. Further, IR may contribute to the pathophysiology of depressive disorder. In conclusion IR could account for the linkage between depression and atherosclerotic vascular diseases. More studies are needed to examine the importance of improving insulin sensitivity in the treatment of chronic-resistant depression and prevention of depression-related vascular morbidity and mortality.