Heart failure (HF) is a common and serious condition that is usually due to coronary artery disease (CAD). Hypercholesterolemia is a major risk factor for CAD but, paradoxically, patients with advanced HF often have low cholesterol, which is associated with a poor prognosis. Cholesterol lowering with statins reduces morbidity and mortality in patients with CAD who do not have HF and might also have improved outcome in patients with HF had they not been excluded from the reported trials. The results of large trials such as the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Insufficienza Cardiaca (GISSI-HF) study addressing the effects of rosuvastatin in HF are keenly awaited. In addition to cholesterol lowering, statins have other biologic effects that might be responsible for some of their favorable effects. This article examines this cholesterol paradox and possible mechanisms.