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Atherosclerosis, the key pathogenesis of cardiovascular disease, is a leading cause of death and disability worldwide. Statins are first-line lipid-lowering drugs, which have been demonstrated to be powerful agents for anti-atherosclerosis. Numerous studies have confirmed the cardiovascular benefits and long-term safety of statins in a wide range of patients. Statins play an indispensable and irreplaceable part in the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). In this article, we summarize the evolution of statins and their role in the treatment of cholesterol. The anti-atherosclerotic mechanism of statins, its efficacy, safety and clinical outcomes in secondary and primary prevention of ACSVD in different patient populations, the combination treatment effects, and guideline recommendations are also detailed. This paper highlights the profound significance of statins as the most successful anti-atherogenic drug in the cardiovascular field.