Low-density lipoprotein cholesterol (LDL-C) is the most important risk factor for developing coronary artery disease (CAD) as evidenced in landmark INTERHEART study. PCSK9 inhibition offers a novel therapeutic mechanism for lowering low-density lipoprotein cholesterol (LDL-C) levels.PCSK9 is a serine protease that binds the LDL receptor (LDL-R) and acts as a chaperone for endocytosis and shuttling the PCSK9-LDLR complex to lysosomes for degradation. In the absence of PCSK9 the LDLR-LDL-C complex dissociates and LDL-R is recycled back to the cell surface. Humanized monoclonal antibodies against PCSK 9 (evolocumab, alirocumab, bocolicumab) have been developed which increase LDL-R by 2- old and lower LDL-C by up to 75 percent with no significant side effects, with the exception of injection site reactions. These novel agents play a pomising role in filling the therapeutic gap in statin intolerant, difficult dyslipidemics and familial hypercholesterolemic patients. When combined with statins they bring out a better cardiovascular outcome with a stable and target lipid profile.