Toxic epidermal necrolysis syndrome (TENS) is a rare, life-threatening medical emergency typically associated with recent drug exposure. Although several theories exist, recent insight has implicated the innate immune system as a significant contributor to the initiation and propagation of this devastating reaction. Standard therapies including transfer to specialized burn units, nutritional support, and protection from infection, remain the mainstay in the treatment of TENS. While alternative treatment strategies have been pursued and reported, there remains no published data that convincingly supports these further interventions. Given the rare nature of this syndrome, multi-institutional studies will be necessary and essential in improving the understanding and treatment of TENS.