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The efficacy of drug therapy results from the complex interplay of multiple processes that govern drug disposition and response. Most studies to date have focused on the contribution of drug-metabolizing enzymes to the drug disposition process. However, over the past decade, it has become increasingly apparent that carrier-mediated processes, or transporters, also play critical roles in the overall disposition of numerous drugs in clinical use. In addition to their roles in xenobiotic transport, drug transporters often mediate important physiologic functions via transport of endogenous substrates such as amino acids, bile acids, and hormones that are critical for maintenance of normal homeostasis. In this review we focus on the emerging field of transporter proteins in relation to the drug disposition process, with particular emphasis on clinical implications of transporters to drug-drug interactions and subsequent development of adverse effects, interindividual variability in drug response, and human disease.