There is convincing evidence that many organic anion transporting polypeptide (OATP) transporters influence the pharmacokinetics and pharmacological efficacy of their substrate drugs. Each OATP family member has a unique combination of tissue distribution, substrate specificity and mechanisms of gene expression. Among them, OATP1B1, OATP1B3 and OATP2B1 have been considered as critical molecular determinants of the pharmacokinetics of a variety of clinically important drugs. Liver-specific expression of OATP1B1 and OATP1B3 contributes to the hepatic uptake of drugs from the portal vein, and OATP2B1 may alter their intestinal absorption as well as hepatic extraction. Accordingly, changes in function and expression of these three OATPs owing to genetic polymorphisms may lead to altered pharmacological effects, including decreased drug efficacy and increased risk of adverse effects. Association of genetic polymorphisms in OATP genes with alterations in the pharmacokinetic properties of their substrate drugs has been reported; however, there still exists a degree of discordance between the reported outcomes in different clinical settings. For better understanding of the clinical relevance of genetic polymorphisms of OATP1B1, OATP1B3 and OATP2B1, the present review focuses on the association of the genotypes of these OATPs with in vitro activity changes and in vivo clinical outcomes of substrate drugs.