Many lipid-lowering drugs improve cardiovascular (CV) outcomes. However, when therapies have been studied in addition to statins, it has been challenging to show an additional clinical benefit in terms of CV event reduction, although overall safety seems acceptable. This debate has been complicated by recent guidelines that emphasize treatment with high-potency statin monotherapy. Combination therapy allows more patients to successfully reach their ideal lipid targets. Further testing of novel therapies may introduce an era of potent low-density lipoprotein decrease without dependence on statins, but until then, they remain the mainstay of therapy.