Proprotein convertase subtilisin/kexin 9 (PCSK9) has been shown to degrade hepatic low-density lipoprotein receptors (LDLR). Gain-of-function mutations promote the development of familial hypercholesterolemia, whereas loss-of-function mutations are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and significant protection against coronary heart disease. The major classes of commonly prescribed lipid-lowering medications, such as statins, increase serum PCSK9 levels, thus PCSK9 inhibition would increase the efficacy of statins on LDL-C lowering. Therefore, PCSK9 is an attractive therapeutic target for the new generation of cholesterol-lowering drugs. Here, we present a brief overview of the development of PCSK9 inhibitors and highlight the effect of currently prescribed LDL-C-lowering drugs on PCSK9, and the strategies that are being explored for its therapeutic inhibition. Current research and clinical trial results indicate that a PCSK9 inhibitor may be an exciting new therapeutic drug for the treatment of dyslipidemia and relevant cardiovascular diseases.