Abstract: Atherosclerotic coronary artery disease accounts for the majority of cause of death in the world. A number of determinants most of them associated with lifestyle starting from early childhood onwards are responsible for Cardiovascular Diseases (CVD). Some risk factors facilitate the development of atherosclerosis, while others participate in the plaques formation, resulting in the manifestation of the disease. The major risk factors for CVD such as those results from metabolic disturbances as in high blood pressure, diabetes, obesity and elevated blood cholesterol levels and life style related factors such as cigarette smoking and lack of physical activity continued to represent the center of investigation for all possible mechanism. However, a host of new mechanisms involving new unconventional risk factors such as air pollutions, immunity and infection are also under extensive investigation. As a result; potential markers for CVD risk stratification have emerged. This study is an attempt to provide an over view of the current understanding of CVD pathophysiology stressing the role of new emerging players in the development of the disease.