This narrative review summarizes the pharmacological properties and clinical efficacy of low-density lipoprotein cholesterol (LDL-C)-lowering drugs used in the treatment of atherosclerotic cardiovascular disease (ASCVD). The review begins with the history of cholesterol-lowering drugs, starting with the discovery of compactin in 1972 and the subsequent development of statins in the 1980s. Ezetimibe, the first drug to inhibit intestinal cholesterol absorption, was approved in 2002. The discovery of PCSK9 mutations and the development of PCSK9 inhibitors, including monoclonal antibodies and small interfering RNA (siRNA), marked a new era in lipid-lowering therapies. Bempedoic acid, an oral adenosine triphosphate citrate lyase inhibitor, was recently approved and has shown efficacy in reducing major adverse cardiovascular events. Statins, the first-line therapy for LDL-C reduction, work by inhibiting HMG-CoA reductase, leading to increased LDL receptor expression and reduced LDL-C levels. They are effective in reducing LDL-C by 20–60%, with rosuvastatin being the most potent. Statins also reduce other lipids and have safety profiles that are generally well-tolerated, though they can cause muscle-related adverse effects and increase the risk of type 2 diabetes. Statins are susceptible to drug interactions, particularly with CYP450 enzymes. Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, reduces LDL-C by about 18–20% when used in combination with statins. It is well-tolerated and has no significant drug interactions. It is effective in reducing LDL-C and is often used in combination with statins for patients who cannot tolerate statins. Monoclonal antibodies targeting PCSK9, such as alirocumab and evolocumab, significantly reduce LDL-C by inhibiting PCSK9, which increases the number of LDL receptors on the liver. These drugs are effective in reducing LDL-C by approximately 55% and are well-tolerated, with minimal adverse effects. They are particularly useful in patients with severe hypercholesterolemia. Inclisiran, an siRNA that targets PCSK9 mRNA, provides long-term LDL-C reduction with a single injection every 6 months. It is effective in reducing LDL-C by up to 55% and has a favorable safety profile. Bempedoic acid, a novel cholesterol synthesis inhibitor, works by inhibiting ACLY and is effective in reducing LDL-C without the muscle-related side effects associated with statins. It is well-tolerated and has a favorable safety profile, making it a useful option for patients who cannot tolerate statins. Overall, these drugs offer various options for LDL-C reduction, with different mechanisms of action and safety profiles, allowing for tailored therapy in patients with ASCVD. The reviewThis narrative review summarizes the pharmacological properties and clinical efficacy of low-density lipoprotein cholesterol (LDL-C)-lowering drugs used in the treatment of atherosclerotic cardiovascular disease (ASCVD). The review begins with the history of cholesterol-lowering drugs, starting with the discovery of compactin in 1972 and the subsequent development of statins in the 1980s. Ezetimibe, the first drug to inhibit intestinal cholesterol absorption, was approved in 2002. The discovery of PCSK9 mutations and the development of PCSK9 inhibitors, including monoclonal antibodies and small interfering RNA (siRNA), marked a new era in lipid-lowering therapies. Bempedoic acid, an oral adenosine triphosphate citrate lyase inhibitor, was recently approved and has shown efficacy in reducing major adverse cardiovascular events. Statins, the first-line therapy for LDL-C reduction, work by inhibiting HMG-CoA reductase, leading to increased LDL receptor expression and reduced LDL-C levels. They are effective in reducing LDL-C by 20–60%, with rosuvastatin being the most potent. Statins also reduce other lipids and have safety profiles that are generally well-tolerated, though they can cause muscle-related adverse effects and increase the risk of type 2 diabetes. Statins are susceptible to drug interactions, particularly with CYP450 enzymes. Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, reduces LDL-C by about 18–20% when used in combination with statins. It is well-tolerated and has no significant drug interactions. It is effective in reducing LDL-C and is often used in combination with statins for patients who cannot tolerate statins. Monoclonal antibodies targeting PCSK9, such as alirocumab and evolocumab, significantly reduce LDL-C by inhibiting PCSK9, which increases the number of LDL receptors on the liver. These drugs are effective in reducing LDL-C by approximately 55% and are well-tolerated, with minimal adverse effects. They are particularly useful in patients with severe hypercholesterolemia. Inclisiran, an siRNA that targets PCSK9 mRNA, provides long-term LDL-C reduction with a single injection every 6 months. It is effective in reducing LDL-C by up to 55% and has a favorable safety profile. Bempedoic acid, a novel cholesterol synthesis inhibitor, works by inhibiting ACLY and is effective in reducing LDL-C without the muscle-related side effects associated with statins. It is well-tolerated and has a favorable safety profile, making it a useful option for patients who cannot tolerate statins. Overall, these drugs offer various options for LDL-C reduction, with different mechanisms of action and safety profiles, allowing for tailored therapy in patients with ASCVD. The review