Background: While the major causes of atherosclerotic cardiovascular disease (CVD) are known, clinical audits continue to show inadequate risk factor control, even in the highest risk subjects. More effective risk estimation methods may help, and advances in this field are outlined. There exist excellent guidelines on CVD prevention, but their very length and complexity may limit their use. Other factors inhibiting guideline implementation are explored. Summary: While new medications continue to be developed, the real challenges to effective CVD prevention are societal and political. Both nationally and at European levels, cohesive, integrated strategies with defined responsibilities and accountability are needed, together with empowerment of people to understand the concept of risk and what they can do about it. Key Messages: There are profound health inequalities between and within countries that need to be addressed.