Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, consistently reduce cardiovascular risk. It has recently emerged that cholesterol reduction is not their only mode of action, with current research largely focused on the pleiotropic effects of statins. These include the improvement of endothelial dysfunction, their anti-inflammatory properties, and the mobilization of bone marrow-derived endothelial progenitor cells. All these effects are potentially beneficial in chronic heart failure (CHF), although prospective trials are needed to confirm this. However, cholesterol reduction by statins per se may prove detrimental in patients with CHF, as cholesterol seems to be able to inactivate endotoxin as a stimulus for proinflammatory cytokine production. It is therefore tempting to speculate that low doses of statins still confer pleiotropic effects without lowering plasma cholesterol levels.