Chronic stress and probably the accompanying changes in personal behaviours can influence life expectancy. The role of adrenocorticotropic hormone (ACTH) and cortisol in atherosclerosis is not widely accepted and incompletely characterized. Several reports support a role of these hormones in atherogenesis by modulating the function of vascular endothelium, the recruitment of circulating monocytes to the artery wall and their differentiation into macrophages- foam cells, by controlling the expression of pro- and anti-inflammatory interleukins. Previous reports suggested an important role of ACTH and cortisol in the modulation of atherosclerotic plaque progression by removal of excess free cholesterol from macrophages. Studies suggested a crucial role of these hormones on the development of acute coronary syndromes [(ACS); unstable angina, and acute myocardial infarction] and stroke, by modulating platelet aggregation and thrombus formation. This review focuses on the identified mechanisms and roles of ACTH and cortisol in atherogenesis, progression of atherosclerosis and the development of ACS. Finally, it proposes experimental studies to evaluate the therapeutic potential of new glucocorticoid antagonists, the effects that may derive from the inhibition cortisol synthesis and the role of 11β-hydroxysteroid dehydrogenase type 1 inhibitors in atherogenesis, progression of atherosclerosis and the development of ACS. These hormones may be a possible additional target for the prevention and treatment of atherosclerosis.