Warfarin is the most widely used oral anticoagulant. Its indication is the prevention or treatment of thromboembolism. Although warfarin is highly effective, it has several limitations because of its narrow therapeutic index and the large inter-individual variability in dosing requirement making it a very problematic drug to prescribe. Several factors can affect the patients response to warfarin. Genetic polymorphisms in cytochrome P450 2C9 (CYP2C9) encoding CYP2C9 enzyme, the major drug metabolizing enzyme of S-warfarin, and vitamin K 2, 3-epoxide reductase complex subunit 1 (VKORC1), the target enzyme of warfarin, taken together with age, body mass index, and drug interactions explained 59% of warfarin dose-response variability. In addition, environmental factors (such as alcohol drinking and smoking) can also affect the variability in warfarin response. The purpose of this review is to gather the knowledge about the pharmacology of warfarin and the factors affecting warfarin response. This useful information will improve the efficacy and safety of warfarin therapy.