This is a case report of a 16-year-old patient with DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) associated with vancomycin who improved with systemic steroid treatment. DRESS syndrome is a life-threatening disease process typically secondary to medications, such as anticonvulsants, sulfonamides, and allopurinol. Vancomycin has also been associated with this condition. Apart from discontinuation of the offending agent, there are no clear treatment guidelines, but reports of improvement with systemic corticosteroids are described. We present a case of a 16-year-old male who had been on vancomycin for greater than 4 weeks before developing symptoms consistent with the diagnosis of DRESS syndrome. Our patient demonstrated marked improvement with systemic corticosteroids.