The metabolism and elimination of drugs is mainly mediated by cytochrome P450 (CYP) enzymes, aided by conjugative enzymes and transport proteins. An integral aspect of this elimination process is the induction of drug metabolism through activation of gene expression of metabolic and transport proteins. There is compelling evidence that induction is regulated by drug-activated nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR). This review outlines the basic properties of CAR and PXR, their ligands and target genes, and the mechanisms of the induction process. The implications of nuclear receptor-mediated induction for drug research are also discussed.