Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characterized primarily by nonspecific systemic symptoms such as fever, a classical rash, and eosinophilia. While this is an adverse reaction more often related to medications such as anticonvulsants, many drugs have been reported to be implicated in this event. We report a case of a 35-year-old male who developed DRESS syndrome within one month of beginning leflunomide therapy. Despite treatment with a prolonged steroid taper, he developed a flare-up with transaminitis less than two months after his initial hospitalization. Our patient was managed with steroid pulse therapy and cyclosporine, which resulted in an improvement of symptoms and transaminitis. To our knowledge, only nine previous cases of leflunomide-induced DRESS syndrome have been previously reported.