Multiple drug resistance is a common problem in the treatment of epilepsy. Among various classes of drug transporters, genetic variants of P-glycoprotein (P-gp) encoded by the MDR1 (Multidrug resistance 1) gene have been associated with drug-refractory epilepsy. The MDR1 gene is highly polymorphic. The studies reported an association of MDR1 single nucleotide polymorphism (SNP) with medically refractory epilepsy. Studies to test the association between MDR1 polymorphisms and drug response in epilepsy have been carried out in ethnically different populations with conflicting results. This article provides a review of the significance of single nucleotide polymorphisms of the MDR1 gene in the development of drug-refractory epilepsy.