Cardiovascular diseases (CVD) are the leading cause of death world-wide. In humans, under atherosclerotic lesion formation is the most prevalent cause of CVD. Although cardiac deaths are common in the great apes, the human form of atherosclerotic heart disease is rarely seen in apes. Because humans and apes are genetically similar, the high-incidence of atherosclerotic disease in humans suggests that human susceptibility to CVD may be related to the maladaptation of ancestral genes to the modern environment. The environmental basis of CVD disease is supported by studies showing that the risk of the disease is rapidly modified by changes in the environment. Several components of the natural, community and personal environments are strong determinants of CVD risk in humans. Aspects of the natural environment such as the day-night cycles, seasonal variations, sunlight, and altitude modify CVD risk. Human CVD risk is also affected by the socioeconomic factors, social networks, the built environment, and neighborhood characteristics. The impact of cultural and social environments that humans live in is transmitted over successive generations to the extent that it appears to an agent of natural selection of genes that regulate cardiovascular function and metabolism. Pollutants, toxic chemicals and changes in the global climate are associated with an increase in CVD risk. In addition, aspects of the personal environment created by lifestyle choices such as diet, physical activity and smoking profoundly affect cardiovascular health. Several studies show that a majority of CVD and diabetes in human populations could be attributed to unhealthy personal lifestyle choices and is, therefore, preventable. A better understanding of the mechanisms by which environmental factors affect CVD risk and mortality will help in designing more effective preventive and therapeutic approaches - not only to decrease risk factor burden but also to promote healthful living.