Purpose of Review: Apart from lifestyle modifications, lipid lowering strategies have become the cornerstone in primary prevention of atherosclerotic cardiovascular disease (ASCVD). Although multiple primary prevention guidelines are available, a significant gap exists between evidence-based guidelines and day-to-day practice. Not only adherence to guideline-based treatment but achieving guideline-directed statin intensity are still suboptimal. Based on recent data, cardiovascular outcome benefits are still observed with profound lowering of low density lipoprotein cholesterol (LDL-C), to levels lower than current guideline goals. With better understanding of signaling molecules, genetics and development of advanced tools, lipid lowering strategies have focused more on biological, RNA-, and gene-related approaches. Recent Findings: Over the last decade, lipid lowering strategies have shifted from targeting HMG-CoA reductase to focusing on the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. By binding with low density lipoprotein receptors (LDL-R) on hepatocytes, the PCSK9 protein blocks the recirculation of the LDL-R and plays an integral role in LDL-C clearance. Data from recent PCSK9 trials show that profound reduction of LDL-C could be achieved with PCSK9 monoclonal antibodies and there is no lower limit of LDL-C below which it does not show cardiovascular risk benefits. Currently, preliminary phase III trials are assessing the safety and efficacy of PCSK9 vaccines with purpose of inducing autoantibody production to neutralize the PCSK9 protein. Phase III trials of small interfering RNA, which interrupts the production of PCSK9 protein, are also ongoing. In addition, a recent PCSK9 gene editing study in primates has shown sustained reduction in LDL-C. Summary: Since ASCVD is a life-long vascular remodeling process, early initiation and aggressive lowering of LDL-C is imperative to achieve sustained benefits in cardiovascular outcomes. Novel lipid lowering therapies targeting the PCSK9 protein, including its neutralization by monoclonal antibodies, halting its production, or targeting the PCSK9 gene itself, are promising lipid management strategies which could prevent and potentially eradicate ASCVD.