PCSK9 monoclonal antibodies are novel lipid-lowering therapy that have been extensively studied in patients with hypercholesterolemia either as monotherapy or as an add-on to other LLTs. PCSK9 monoclonal antibodies have significantly reduced the low-density lipoprotein cholesterol (LDL-C) plasma level resulting in a better LDL-C goal attainment. The commercially available PCSK9 monoclonal antibodies, alirocumab and evolocumab, have demonstrated reductions in major adverse cardiovascular events such as myocardial infarction, stroke, unstable angina, and the need for coronary revascularization but not mortality. PCSK9 monoclonal antibodies have demonstrated a favorable safety profile. The most reported side effects are mild injection site with no causal relationship proven between the inhibition of PCSK9 and neurocognitive or glycemic adverse events. In this overview, the efficacy and safety of PCSK9 monoclonal antibodies in the treatment of primary and familial hypercholesterolemia will be discussed.