PURPOSE OF REVIEW: Atherosclerotic cardiovascular disease (ASCVD) remains a leading global health challenge, with low-density lipoprotein (LDL) cholesterol a pivotal risk factor. While statins are cornerstone therapy for lowering LDL cholesterol, many high-risk primary prevention patients are unable to tolerate statin therapy and do not achieve their guideline directed LDL cholesterol goal. For these patients, non-statin therapies offer complementary and alternative approaches to LDL cholesterol reduction. RECENT FINDINGS: Recent advancements in non-statin therapies have expanded the options available to clinicians to lower LDL cholesterol in high-risk primary prevention patients. Yet these medications are often under-utilized in clinical practice. Observational studies, Mendelian randomization studies, and randomized clinical trials support the role of non-statin LDL cholesterol lowering therapies in the primary prevention of ASCVD. This review summarizes the evidence supporting their use for the primary prevention of ASCVD and offers practical suggestions as to how clinicians can integrate these medications into their clinical practice.