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P-glycoprotein (PGP) is well known because of its contribution to multiple-drug resistance during anticancer treatment. More recent work indicates that PGP mediates the transcellular transport of many drugs in addition to anticancer compounds. Because of this reason, its potential role in clinically significant drug-drug interactions has just begun to be realized. This article provides an overview of published in vitro, in situ, and in vivo drug-drug interaction results that are related to PGP transport so that the awareness of the scientific community can be heightened. In addition, several recommendations are made to take full advantage of the recently published data.