Toxic epidermal necrolysis (TEN) is an acute, rapidly evolving mucocutaneous reaction with a high mortality rate characterized by extensive painful cutaneous and mucosal exfoliation and systemic involvement that is frequently associated with medication use. The treatment of this condition is controversial. Systemic lupus erythematosus (SLE) is a generalized autoimmune disease of unknown etiology characterized by the production of autoantibodies to self antigens. Several case reports in the literature have demonstrated an association between SLE and TEN, and it has been postulated that lupus-associated TEN may exist. In this review, we will explore the association of SLE and TEN, and its diagnosis and treatment.