The processes involved in discovering, developing, and testing new drugs often focus on detailed refinement of chemistry or engineering practice, which result in small, albeit clinically valuable, improvements in the management of a particular disease state. But just occasionally, either through serendipity or insightful creativity, or both, a series of new compounds comes to light whose uniqueness of action revolutionizes the management of a hitherto intractable clinical problem. Such was the case when pharmacology unveiled the wide-ranging portfolio of lipidlowering agents, which for the first time has allowed us to control the worst excesses of dyslipidemia in our patients. Here we consider the discovery and review the clinical merits of the statins, ezetimibe, the peroxisome proliferator activated receptor (PPAR) agonists, and nicotinic acid...