The pregnane X receptor (PXR) is a nuclear receptor that is activated by a spectrum of structurally unrelated endogenous compounds and clinical drugs. Expressed predominantly in the liver and intestine, activated PXR in conjunction with the retinoid X receptor (RXR) plays a central role in drug metabolism by inducing the cytochrome P450 family of enzymes. This includes the induction of CYP3A4, an enzyme responsible for the phase I metabolism of more than 50% of drugs in use today. In addition, PXR/RXR activation induces drug conjugation enzymes as well as the drug efflux pumps. Thus, PXR is an important regulator of drug metabolism and excretion. PXR/RXR activation can also regulate several endogenous processes like bile acid synthesis, their metabolism and transport, gluconeogenesis, lipid metabolism and cholesterol homeostasis. Thus the PXR/RXR heterodimer plays a fundamental role by regulating the expression of a critical set of protective gene products involved in xenobiotic and endobiotic metabolism.