The toll-like receptors (TLRs) are a class of transmembrane-spanning receptors that are sentinels of both innate and adaptive immunity. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the most commonly prescribed therapeutic agents for treating hypercholesterolemia globally. However, statin therapy appears to have pleiotropic effects including attenuation of chronic low-grade inflammation and modulation of TLR activity. Statins through abolition of TLR4 expression and regulation of the TLR4/Myd88/NF-κB signaling pathway may slow the progression of atherosclerosis and other inflammatory diseases. In this review, we have focused on the impact and mechanism of action of statins on cardiovascular and non-cardiovascular diseases.