On the basis of seminal genetic discoveries, proprotein convertase subtilisin/kexin Type 9 (PCSK9) inhibitors were developed as a new class of LDL cholesterol-lowering drug, with a potency on par with and on top of high-intensity statins and an excellent safety profile. A series of large cardiovascular outcomes trials have now established the ability of monoclonal antibody PCSK9 inhibitors to reduce the risk of major adverse cardiovascular outcomes across a broad range of patients, including those with a prior major atherosclerotic cardiovascular disease (ASCVD) event, those with atherosclerosis but without a prior major ASCVD event, and those with diabetes. Moreover, these trials have shown the clinical benefit of lowering LDL cholesterol to ∼1 mmol/L (∼40 mg/dL) in such patients. New members of this class are being studied including oral inhibitors, RNA interference, and gene therapy.