Major clinical evidence obtained in the last 15-20 years with statins is reviewed. A tight correlation between LDL cholesterol and occurrence of major cardiovascular events has been observed. Moreover, favorable effects have been shown also in subjects with normal cholesterol blood levels and high levels of high-sensitivity C-reactive protein (hsCRP), a predictive marker of cardiovascular events. In two studies involving patients with acute coronary artery disease the prognosis was better in subjects with cholesterol levels < 70 mg/dl or hsCRP < 2 mg/I. These studies provide the background for the JUPITER trial, a double-blind randomized controlled "globalized" study with rosuvastatin 20 mg in primary prevention, including 17 802 normal cholesterolemic males and females with increased risk for hsCRP > 2 mg/I. The combined primary endpoint included myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Rosuvastatin reduced LDL cholesterol levels by 50% and hsCRP levels by 37%. The trial was stopped after a median follow-up period of 1.9 years, due to a significant superiority of rosuvastatin on the incidence of major cardiovascular events. Moreover, long-term adherence to randomized treatment was excellent, and safety was consistent in the two groups. Eligible patients were more than one fourth of the outpatients attending a cardiology clinic; median age of 66 is 5-6 years lower than age of patients admitted to Italian intensive cardiac care units for acute coronary disease, suggesting the usefulness of a primary prevention program with rosuvastatin in this clinical setting. Practical and healthcare planning implications deriving from this study are currently under evaluation by scientific societies and healthcare authorities.