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RNA-based therapies have emerged as a transformative approach in the management of hypercholesterolemia and coronary artery disease by directly targeting molecular pathways involved in lipid regulation. These treatments focus on silencing key genes such as PCSK9, ANGPTL3, ApoB, and Lp(a), achieving substantial reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, and other atherogenic lipoproteins. Small interfering RNA (siRNA) and antisense oligonucleotides (ASOs) provide highly specific post-transcriptional gene suppression, while advances in chemical stabilization and GalNAc conjugation have enhanced hepatocyte delivery and prolonged therapeutic action. Approved agents such as inclisiran demonstrate sustained LDL-C reductions of approximately 50% with only two to three injections annually, improving adherence and offering an alternative for patients intolerant to statins or unable to reach lipid targets with conventional therapy. Pelacarsen and other emerging antisense therapies show promise for reducing lipoprotein(a), an independent cardiovascular risk factor, while siRNAs targeting ANGPTL3 offer prolonged lipid-lowering effects beyond those achieved with monoclonal antibodies. Despite these advantages, challenges remain. Hepatic safety concerns have halted the development of some agents, such as vupanorsen, and long-term cardiovascular outcome data for several therapies, including inclisiran, are still in development. Cost and accessibility also limit broad adoption, emphasizing the need for cost-effective strategies and long-term surveillance. Nevertheless, current evidence supports the integration of RNA-based therapies into modern lipid-lowering algorithms, particularly for high-risk patients, while ongoing research continues to refine delivery systems, enhance safety, and expand therapeutic indications.