A 23-year-old human immunodeficiency virus (HIV)-infected Indian woman was admitted to a tertiary care hospital with generalized erythematosus rash all over her body with difficulty in swallowing for the previous 3 days. She also presented with swelling of the lips and redness of both eyes along with nausea, anorexia, slight headache, and fever, which appeared immediately after the initiation of a new regime of antiretroviral treatment with tenofovir (300 mg once daily), lamivudine (300 mg once daily), and efavirenz (600 mg once daily). Presumptive diagnosis of efavirenz-induced Stevens-Johnson syndrome was made after excluding other causes. Efavirenz was withdrawn, followed by tenofovir and lamivudine. Supportive care was provided to the patient during her hospital stay. She recovered after 2 weeks. Thus, strict vigilance of adverse drug reaction is required in patients on a highly active antiretroviral therapy regimen.