Organic anion-transporting polypeptides (OATPs) are a superfamily of uptake transporters that mediate the cellular uptake of a broad range of endogenous and exogenous compounds. Of these OATP transporters, members of the 1A and 1B subfamilies have broad substrate specificities. Because they are mainly expressed in liver, kidney and small intestine, OATP1A and 1B transporters can have a major impact on the pharmacokinetics of many drugs. To study their role in physiology and drug disposition, several mouse models lacking functional expression of one or more OATPs have been generated. This review discusses recent findings for these models that have led to new insights into the impact of OATP1A and 1B transporters on pharmacokinetics and toxicokinetics, and on bilirubin detoxification and bile acid handling in normal liver physiology.