Statin therapy has revolutionized the management of patients at risk for ischemic events due to dyslipidemia. Large-scale trials show that statins reduce cardiovascular mortality across various patient groups. However, the exact mechanism of their benefit remains debated. The causal theory suggests that statins lower lipid levels, which reduces atherosclerosis. The noncausal theory posits that statins have pleiotropic effects, such as improving endothelial function, inflammation, coagulation, and plaque stability, which are major factors in clinical benefit. This review focuses on these pleiotropic effects and their role in reducing ischemic risk. The endothelium regulates vascular tone through vasoconstrictor and vasodilator compounds. Dyslipidemia impairs endothelial function, but statins can restore it. Pravastatin improves endothelial function by activating endothelial nitric oxide synthase (eNOS), independent of cholesterol lowering. Atorvastatin and simvastatin reduce endothelin-1 levels, a vasoconstrictor, and increase nitric oxide production. Statins also reduce atherosclerotic lesion size by decreasing smooth muscle cells, macrophages, and fibrinogen. Nitric oxide synthase-II (NOS-II) is positively correlated with lesion size and inversely related to HDL levels. Statin therapy improves nitric oxide production, which reduces atherosclerotic lesion extent. In clinical trials, fluvastatin improved endothelial-dependent dilation in hypercholesterolemic patients. It also increased forearm blood flow in response to reactive hyperemia, indicating improved endothelial function. Combination therapy with other drugs has shown additional benefits. In summary, statins reduce cardiovascular risk through lipid-lowering and pleiotropic effects, particularly by improving endothelial function, reducing inflammation, and stabilizing plaques. These effects contribute to the overall benefit of statin therapy in preventing ischemic events.Statin therapy has revolutionized the management of patients at risk for ischemic events due to dyslipidemia. Large-scale trials show that statins reduce cardiovascular mortality across various patient groups. However, the exact mechanism of their benefit remains debated. The causal theory suggests that statins lower lipid levels, which reduces atherosclerosis. The noncausal theory posits that statins have pleiotropic effects, such as improving endothelial function, inflammation, coagulation, and plaque stability, which are major factors in clinical benefit. This review focuses on these pleiotropic effects and their role in reducing ischemic risk. The endothelium regulates vascular tone through vasoconstrictor and vasodilator compounds. Dyslipidemia impairs endothelial function, but statins can restore it. Pravastatin improves endothelial function by activating endothelial nitric oxide synthase (eNOS), independent of cholesterol lowering. Atorvastatin and simvastatin reduce endothelin-1 levels, a vasoconstrictor, and increase nitric oxide production. Statins also reduce atherosclerotic lesion size by decreasing smooth muscle cells, macrophages, and fibrinogen. Nitric oxide synthase-II (NOS-II) is positively correlated with lesion size and inversely related to HDL levels. Statin therapy improves nitric oxide production, which reduces atherosclerotic lesion extent. In clinical trials, fluvastatin improved endothelial-dependent dilation in hypercholesterolemic patients. It also increased forearm blood flow in response to reactive hyperemia, indicating improved endothelial function. Combination therapy with other drugs has shown additional benefits. In summary, statins reduce cardiovascular risk through lipid-lowering and pleiotropic effects, particularly by improving endothelial function, reducing inflammation, and stabilizing plaques. These effects contribute to the overall benefit of statin therapy in preventing ischemic events.