The potential of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ('statins') to reduce the incidence and/or progression of certain malignancies remains uncertain. Some investigators have concluded that statins have no effects on malignancies of any kind. However, results of several epidemiologic studies, including four recent prospective cohort studies, suggest that long-term statin therapy inhibits the progression of prostate cancer. We argue that the principal mechanism of any anticancer effects from statin use arises from prolonged lowering of circulating cholesterol. Evidence suggests that prostate cancer might be particularly sensitive to this intervention. Our hypothesis provides a perspective from which mechanistic studies of cholesterol-lowering drugs and cancer, in addition to prospective trials in patients, might be designed.