Objective: To evaluate the safety and efficacy of 2 human monoclonal antibodies, alirocumab and evolocumab, on reduction of low-density lipoprotein cholesterol (LDL-C), cardiovascular benefits, and their place in current practice. Data Sources: A search of MEDLINE and Scopus databases (1966 to May 2016) with search terms “alirocumab,” “evolocumab,” “LDL,” and “PCSK9.” Study Selection and Data Extraction: The search identified phase 3 randomized control trials in English language in the past 10 years that studied LDL-C reduction of alirocumab or evolocumab. The studies were assessed for all efficacy and safety endpoints. Data Synthesis: Twelve total studies were identified evaluating alirocumab or evolocumab. These monoclonal antibodies have been shown to significantly decrease LDL-C as monotherapy and in combination with statins in phase 3 clinical trials in patients with primary hypercholesterolemia as well as familial hypercholesterolemia by inhibiting PCSK9. Alirocumab significantly reduced LDL-C by up to 61%, while evolocumab significantly reduced LDL-C by up to 66%. Adverse effects of these medications have been low and overall well tolerated. Conclusion: Although these monoclonal antibodies have shown to significantly reduce LDL-C, their effect on cardiovascular outcomes has not yet been determined. Further studies are being conducted to assess the cardiovascular benefit of both alirocumab and evolocumab. Until these studies demonstrate a reduction in atherosclerotic cardiovascular disease risk, statins should remain first-line therapy for most patients. However, alirocumab and evolocumab can be used as an effective adjunctive therapy option to lower LDL-C or in patients who are statin intolerant.