Human body needs to protect itself from a diverse array of harmful chemicals. These chemicals are also involved in drug metabolism, enzyme induction, and can cause adverse drug-drug interactions. Being a member of nuclear receptors (NRs), pregnane X receptor (PXR) has recently emerged as transcriptional regulators of cytochrome P450 (CYP) and transporters expression so as to against xenobiotics exposure. This review describes some common nuclear receptors, i.e. farnesoid X receptor (FXR), small heterodimer partner (SHP), hepatocyte nuclear factor-4alpha (HNF-4alpha), liver X receptor (LXR), glucocorticoid receptor (GR), constitutive androstane receptor (CAR) that crosstalk with PXR and involvement of coregulators thus control target genes expression.