Stevens-Johnson Syndrome (SJS), or erythema multiforme, is a severe, acute, adverse, cutaneous reaction to certain medications, such as phenytoin and topical nitrogen mustard. The risk of developing SJS is high when phenytoin and steroids are administered during cranial irradiation. SJS produces headache, malaise, sore throat, fever, and sloughing of the skin and mucous membranes. Prompt recognition of SJS and withdrawal of the offending medication is key to treating this disorder. Nurses play an important role in assessing patients and educating them about signs and symptoms of SJS.