The recently completed study Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) demonstrates that statin therapy reduces vascular events in apparently healthy men and women with low levels of low-density lipoprotein cholesterol (mean, 104 mg/dL) who are at elevated risk due to high-sensitivity C-reactive protein levels greater than 2 mg/L. Among 17,802 trial participants, rosuvastatin resulted in a 44% reduction in the primary end point of all vascular events (P < 0.00001), a 54% reduction in myocardial infarction (P = 0.0002), a 48% reduction in stroke (P = 0.002), a 46% reduction in need for arterial revascularization (P < 0.001), and a 20% reduction in all-cause mortality (P = 0.02). All subgroups with elevated high-sensitivity C-reactive protein benefited, including those traditionally considered to be at low risk, such as women, nonsmokers, and those with Framingham risk scores less than 10%. Absolute risk reductions within JUPITER result in a number needed to treat at 5 years of 25, a value comparable or superior to that of other interventions routinely used in primary prevention, including statin therapy among those with hyperlipidemia. Although lifestyle interventions remain critical, the screening and treatment strategy tested in JUPITER is likely to impact on new guidelines for cardiovascular disease prevention.