The chronic idiopathic inflammatory bowel diseases (IBDs), Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by an overly aggressive cell-mediated immune response to luminal commensal bacteria in genetically susceptible individuals. 1, 2 Several lines of evidence now suggest a role for the multidrug resistance (MDR1) gene and its product P-glycoprotein 170 (PgP) in the regulation of host–bacteria interaction and in the pathogenesis of IBD. PgP functions as an ATP-dependent efflux transporter pump and is highly expressed in the epithelial surfaces of intestine, biliary ductules, proximal tubules of kidneys, and central nervous system, where it forms the basis of the blood–brain barrier. 3–5 Interindividual variability of PgP expression in the intestine plays a role in the determining the pharmacokinetics of a wideranging number of substrates. 6 The exact physiological role in the gut remains unknown. The high constitutive levels of expression of PgP in the gut suggest a role in protection against xenobiotics and bacterial products. 7 This review focuses on the current data (animal studies, gene expression, and genetic studies) on the possible role of MDR1 in IBD and also future directions and implications of our current knowledge of this gene.