On the basis of large randomized trials, current guidelines recommend to treat all patients with type 2 diabetes or coronary artery disease after myocardial infarction with statin drugs. However, the recent 4D, CORONA and GISSI-HF trials show that old patients with ischemic heart failure and patients with diabetes and end-stage renal disease on hemodialysis do not benefit from new onset of statin therapy with regard to mortality. The survival benefit from statin therapy appears to stem primarily from the prevention of progression of coronary artery disease. In clinical conditions where coronary artery disease does not significantly contribute to the cause of death, statins seem to be less effective. In patients at risk of organ damage, statin therapy therefore has to be initiated early in the course of the disease. The effect of statin withdrawal in ischemic heart failure or in patients with advanced renal disease is not known and potentially harmful and therefore, on the basis of the available evidence, ongoing statin treatment should not be stopped in these patients.