Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, powerfully lower total cholesterol and low-density lipoprotein cholesterol (LDL-C). Stereochemical similarities in the primary mechanisms of action, competitive inhibition of the HMG-CoA reductase active site, and results of early large-scale clinical trials over the last two decades helped to reinforce a widespread concept of the class effects of statins as generally similar agents. Development of ever-more potent second- and third-generation statins have offset this initial uniform statin class-effect concept, perhaps fuelled by cerivastatin’s withdrawal from the market due to an exceptionally high incidence of severe muscle toxicity, especially in combination with gemfibrozil. At the same time, the notion that statins may not differ in terms of safety has also persisted. A comparative review of metabolism and drug–drug-interactions of pitavastatin, the most recent addition to the class, and other statins may help further differentiate different agents, with special reference to safety.