Atherosclerotic disease is considered to be the leading cause of death and loss of disability-adjusted life-years worldwide. Major differences are between different countries, mainly because of the variation of risk factors for atherosclerosis between populations. Over 300 risk factors have been associated with atherosclerosis and its major complications, coronary heart disease and stroke. However, between 70% and 90% of the risk of atherosclerotic disease can be explained by different associations between conventional risk factors, such as smoking, abnormal lipids, hypertension, diabetes, obesity, psychosocial factors, unhealthy diet, and lack of physical activity. Because risk factors can have multiplicative effects, their assessment in an individual subject needs application of different models for total risk estimation. Effective cardiovascular prevention needs a global strategy, based on knowledge of the importance of different risk factors, conventional and newly-described, and of the best model that can be applied to assess risk for atherosclerotic disease in an individual subject.