Toxic epidermal necrolysis (TEN) is a life-threatening, drug-induced disorder characterized by severe epidermal injury. Although there is no standard therapeutic intervention in TEN, plasmapheresis (PP) is being used increasingly to treat extremely ill TEN patients. In addition to conventional PP, double-filtration PP (DFPP) has been recently used for severe and refractory TEN. In this review, we focus on the clinical usefulness of PP by both demonstrating three cases of TEN refractory to conventional therapies, who were successfully treated with conventional PP or DFPP, and evaluating its therapeutic efficiency. We also provide evidence to suggest the mechanisms of action of PP by investigating the correlation between disease intensity and serum cytokine levels before and after treatment with PP or DFPP in these patients with TEN. At present, PP is a much more effective option for treatment of severe and/or recalcitrant TEN than any other treatment, such as pulsed corticosteroids and i.v. immunoglobulin.