Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are potentially life-threatening type IV immune reactions characterized by systemic inflammation mediated by cytotoxic T lymphocytes resulting in epidermal detachment and extensive necrosis. Although infrequent, the main concern across the SJS/TEN spectrum is its mortality, morbidity and associated financial burden. To date, there are no definitive recommendations regarding optimal treatment regimens; therefore, early diagnosis, prompt withdrawal of the culprit drug, and interdisciplinary consultations are vital to avoid disease progression. It is hard to assess the efficacy of novel therapies when the “conventional”, well-founded therapies with corticosteroids and cyclosporine are still under investigation. However, optimal posology is still under debate, as well as possible combined therapies. Other drugs that have shown to have a possible beneficial effect, like etanercept and n-Acetylcysteine, are still under investigation, given the insufficient number of investigations and small samples. New pharmacological approaches have been proposed in the last decade to improve outcomes across the SJS/TEN spectrum. This review aims to analyze novel approaches for SJS/TEN and assess their efficacy and safety compared to currently available treatments.