3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are among the most commonly prescribed and studied drugs in modern medicine. Their proven benefit in prevention of cardiovascular events is driven by their ability to markedly reduce low-density lipoprotein cholesterol (LDL-C). Recent analyses have provided insight into the relationship between statin-induced reductions in LDL-C and risk of rhabdomyolysis, liver toxicity, and cancer. Risk of statin-associated elevated liver enzymes and rhabdomyolysis is not related to the magnitude of LDL-C lowering. Instead, drug- and dose-specific effects of statins are more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, although there is an inverse association between LDL-C and cancer risk in both statin-treated and comparable control cohorts, statin therapy, despite significantly reducing LDL-C, is not associated with an increased risk of cancer.