High cholesterol is often a prerequisite for atherosclerotic plaque. Low-density lipoprotein cholesterol (LDL-C) is the focus of the National Cholesterol Education Program Adult Treatment Panel guidelines. LDL-C ranges from 50 to 70 mg/dL in native hunter-gatherers, healthy human neonates, free-living primates, and other wild mammals, who are notably free of atherosclerotic vascular disease. Multiple statin trials and meta-analyses support a treatment target of LDL-C levels less than 70 mg/dL, as this is associated with improved clinical outcomes and atherosclerosis regression. In fact, no threshold has yet been identified below which patients do not benefit from lowering of LDL-C.