Establishing the methods for the effective screening of compounds with optimal pharmacokinetic properties is of great importance to many scientists working in new drug discovery and development. This review deals with the methods by which in vivo pharmacokinetics in humans can be predicted from in vitro studies and from in vivo animal experiments. Direct extrapolation from animal studies to human pharmacokinetics is generally difficult because of species differences in the function of molecules involved in drug metabolism and transport. To overcome this problem, a "scaling factor," which relates in vivo animal studies with in vitro experiments, is often used for the accurate prediction. Several experimental systems for the functional analyses of membrane transporters have been developed and many reports have revealed that various transporters clearly govern the tissue dispositions of drugs in humans. This review covers the impact of membrane transporters on the pharmacokinetics, control of elimination pathways, and toxicity. Indeed, by utilizing transporter-deficient animals, some studies have clarified the importance of transporters in various types of tissue-specific toxicity. Transporter-mediated drug-drug interactions are one of the most important issues in clinical situation because some reports suggested that severe clinical incidents are caused by the inhibition of transporter-mediated uptake and efflux in clearance organs (liver and kidney) and at several barriers. The review also focuses on the clinical significance of genetic polymorphisms of transporters, as these can influence the plasma and tissue concentrations of some drugs. Finally, integrated information is presented based on multiple in vitro studies, including those on transporters. This should enable the prediction of the outcomes of drug exposure in cells, tissues, and individual organisms.