Multidrug resistance is one of the most serious problems in the treatment of epilepsy and is likely to have a complex genetic and environmental basis. Various experimental data support the hypothesis that overexpression of antiepileptic drug transporters may be important. However, key questions concerning their functionality remain unanswered. The first study reporting a positive association--between genetic variation in a putative antiepileptic drug transporter (P-glycoprotein, encoded by ABCB1) and multidrug resistant epilepsy was published in 2003. Since then, several other association genetics studies have sought to confirm this result, but, taken overall, do not support a major role for this polymorphism. Lessons learnt from the ABCB1 studies can help guide future association genetics studies, both for multidrug resistance in epilepsy, and for other epilepsy phenotypes.