Coronary artery disease is still associated with high morbidity and mortality in Western countries. Lipid blood levels have a tight correlation with the risk of coronary events, and the results of many trials on lipid-lowering therapy (and particularly on simvastatin) demonstrated a significant reduction in total and cardiac mortality, and in the incidence of myocardial infarction and coronary events; even the progression of coronary stenosis has been reduced by treatment with statins. Beyond cholesterol reduction, simvastatin exerts many favorable effects on endothelial function, inflammatory activity, expression of pro-thrombotic factors and oxidative stress, yielding a rational basis for its important clinical positive effects, both in primary and secondary prevention of coronary disease. Future developments, which are the subjects of many planned or ongoing clinical trials, are related to the treatment of high-risk patients, the evaluation of the efficacy of elevated simvastatin dosages and of a deep reduction in cholesterol blood levels, the interaction between simvastatin and other drugs (antioxidant compounds, vitamins, antiplatelet drugs) or interventional procedures (percutaneous transluminal coronary angioplasty). Particularly, the Heart Protection Study, the A to Z trial, and the SEARCH and SMART studies will provide important data on a wider, earlier and greater use of simvastatin, which has been demonstrated effective both in the prevention and treatment of acute coronary syndromes.