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Atherosclerosis is a disease that causes medium-size and larger blood vessels in the body to harden and narrow which is not a clinical symptoms but it is the ultimate stage of any types of coronary heart disease like stroke, heart attack, myocardial infarction, paralysis and so on. In recent decades, there has been increasing interest in exploring the relationship between psychological stress and various health conditions. Extensive studies support that behavioral and psychological factors contribute significantly to the development and progression of atherosclerosis. Psychological factors, specifically depression, anxiety, personality factors, social isolation, and chronic and sub-acute life stress, are known to be related to the risk of heart disease. This spurred on the relentless effort to explore how behaviour and biological systems could interact in the endeavour to uncover more mysteries of the human body. This review addresses the biomolecular mechanism of understanding the role of chronic psychological stressors on the immune system and development of atherosclerosis as well as established the relationship between the chronic psychological stress and the atherosclerosis.