Drug-drug interactions lead to lethal toxicities. Currently P-glycoprotein also plays significant role in drug-drug interactions. It is an efflux membrane transporter widely distributed throughout the body and is responsible for limiting the cellular uptake and the distribution of xenobiotics and toxic substance. The pharmacokinetics of a drug may be altered when co-administered with compounds which inhibit or induce P-glycoprotein pump which can affect pharmacodynamic and pharmacokinetic action of drugs. The present review summarizes various drug-drug interactions mediated by P-glycoprotein transporter.