Purpose: Telaprevir has been increasingly used in combination with pegylated interferon and ribavarin for the treatment of chronic hepatitis C, genotype 1. Skin rash is the most common side effect of telaprevir, as it can occur in 56% of patients, compared to 34% taking ribavarin or interferon alone. It is usually mild in nature, and rarely a cause of treatment cessation. However, about 3.7% of patient have reported severe rashes, sometimes requiring discontinuation of the medication. We present a case of drug-induced rash with systemic eosinophilia (DRESS) syndrome secondary to telaprevir use. A 56-year-old Caucasian male with history of chronic HCV and genotype 1a presented to the medical emergency room with complaints of fatigue and the presence of a generalized rash. He had been started on treatment with pegylated interferon, telaprevir, and ribavarin 10 weeks prior. On initial triage, the patient's blood pressure was 113/60 mm Hg, and body temperature was 100.3 degrees Fahrenheit. Physical examination was remarkable for an exanthematous rash on his trunk and limbs, with a few dispersed pustules on his neck and chest. There was significant cervical lymphadenopathy, along with trace pedal edema bilaterally. Laboratory results revealed leukocytosis, with a white blood cell count of 13.8, with 30% eosinophils, and a serum creatinine of 1.6 mg/dL. Given the history of telaprevir use and the new onset of a rash with a profound eosinophilia, along with what appeared to be systemic involvement, the diagnosis of DRESS syndrome was made. The patient was started on systemic steroids, and telaprevir was immediately discontinued. Over the next few days, the patient noted a marked improvement in his skin rash, and laboratory parameters including eosinophilia and creatinine returned to baseline. In rare instances, telaprevir use can lead to the progression of DRESS syndrome; a serious and potentially fatal drug reaction. DRESS syndrome can manifest as general exanthema, fever, generalized lymphadenopathies, eosinophilia or atypical lymphocytosis and end organ damage. Mortality rates from DRESS syndrome can be as high as 10%. DRESS syndrome may often pose a diagnostic challenge, as skin eruptions and varied organ involvement may differ in patients. Clinicians should maintain a high index of suspicion for DRESS syndrome in patients treated with telaprevir that present with new skin lesions, fever, and the development of systemic symptoms or evidence of end-organ damage. Treatment includes prompt withdrawal of the drug and initiation of corticosteroids. In severe cases, the initiation of intravenous immune globulins may be the treatment of choice.