Cardiovascular disease (CVD), specifically coronary atherosclerosis, is regulated by an interplay between genetic and lifestyle factors. Most recently, a factor getting much attention is the role epigenetics play in atherosclerosis; particularly the development of coronary artery disease. Furthermore, it is important to understand the intricate interaction between the environment and each individual genetic material and how this interaction affects gene expression and consequently influences the development of atherosclerosis. Our main goal is to discuss epigenetic regulations; particularly, the factors contributing to coronary atherosclerosis and their role in aging and longevity. We reviewed the current literature and provided a simplified yet structured and reasonable appraisal of this topic. This role has also been recently linked to longevity and aging. Epigenetic regulations (modifications) whether through histone modifications or DNA or RNA methylation have been shown to be regulated by environmental factors such as social stress, smoking, chemical contaminants, and diet. These sensitive interactions are further aggravated by racial health disparities that ultimately impact cardiovascular disease outcomes through epigenetic interactions. Certainly, limiting our exposure to such causative events at younger ages seems our “golden opportunity” to tackle the incidence of coronary atherosclerosis and probably the answer to longevity.