Statin therapy has been conclusively shown to offer patients clinical benefit, virtually irrespective of their baseline risk status. However, the absolute risk reductions observed in different clinical trials, which have recruited patients across a spectrum of lipid levels and vascular disease states, show that baseline global risk determines the absolute benefit gained and in turn will specify the number of patients needed to be treated in order to realize this benefit. Global risk assessment is therefore central to the clinically meaningful use of statin therapy, and a strong case is now argued in the literature for a high-risk primary prevention strategy that goes hand in hand with standard secondary prevention. The routine use of Framingham-based risk assessment tools is advocated because these are the most widely evaluated and have been repeatedly shown to predict the risk of coronary heart disease accurately in western populations. The risk threshold in primary prevention that should determine pharmacological intervention is the subject of controversy. The currently used annual risk figure of 3% would clearly capture all very high-risk individuals but would also deny treatment to many individuals who will subsequently die from their first coronary event. Although a 1.5% annual risk threshold is economically untenable in the present UK health system, a level of 2% is, we believe, both achievable and affordable.