Among 4 known cytochrome P450 (CYP) 2C genes, CYP2C9 is the most abundantly expressed in the human liver and intestine. CYP2C9 involves in the metabolism of wide variety of clinically used drugs including anticoagulant warfarin, antidiabetic tolbutamide, anticonvulsant phenytoin, hypertensive agent losartan, and several nonsteroidal anti-inflammatory drugs. More than 36 single nucleotide polymorphisms (SNPs) have been identified in human CYP2C9 at present. Two known allelic variants CYP2C9*2 and CYP2C9*3 have been reported to be associated with development of clinically significant adverse reactions, such as life-threatening bleeding episodes with warfarin use and the severe toxicity with phenytoin. Further clinical studies are required for the recently found defective CYP2C9 SNPs, such as CYP2C9*4, *5, *6, *9, *11, *13, *15 and *25. The present report reviews the current progress in the identification and functional studies of CYP2C9 SNPs and the clinical relevance of CYP2C9 genotype on the personalized pharmacotherapy.