In the last 20 years clinical trials evaluating statins showed the importance of LDL-cholesterol lowering in decreasing the risk of cardiovascular disease. The efficacy of statin therapy has been well documented both in primary and secondary prevention, in patients with subclinical atherosclerosis and in those with average cholesterol levels. However, the so-called "residual risk" remains significant and new strategies are needed for reducing it, such as raising HDL-cholesterol levels. Recently, the JUPITER study demonstrated the efficacy of statins in reducing the risk in healthy subjects with elevated C-reactive protein levels, highlighting the potential protective mechanisms of these drugs. Different from the setting of primary and secondary prevention, the results of statin trials in patients with heart failure, end-stage renal disease and aortic stenosis have shown no benefit in terms of survival.