There is little published experience with the extracorporeal treatment of valproic acid overdose, although the pharmacokinetic properties of valproic acid suggest a potential role for hemodialysis and/or hemoperfusion. At therapeutic concentrations valproic acid is highly protein bound, but at the higher concentrations seen in the overdose setting binding sites become saturated and free valproic acid should be subject to removal by hemodialysis. We report the case of a patient with serious toxicity secondary to valproic acid overdose who was successfully treated with a combination of hemodialysis and hemoperfusion. With this treatment the half-life of valproic acid was reduced from a predialysis level of 13 hours to 1.7 hours, with rapid lowering of valproic acid levels and dramatic clinical improvement. Based on our experience in this patient and a review of previously reported cases, hemodialysis should be considered in the treatment of valproic acid overdose.