Rifampicin is a widely used drug to treat tuberculosis and leprosy. Its toxicity is predominantly hepatic and immunoallergic in character. While hepatic toxicity is dose-related, the immunoallergic effects are unpredictable and usually associated with intermittent therapy. These immunoallergic effects may be minor (a cutaneous, gastrointestinal, or influenza-like syndrome) or major (hemolytic anemia, shock, or acute renal failure). Herein, we report a case of rifampicin allergy in a patient who was on intermittent once monthly rifampicin therapy for neuritic leprosy and was on his 4th month of treatment. Rifampicin exposure led to sudden shock and acute renal failure, which eventually required hemodialysis support. The patient made a complete recovery over the subsequent days and his renal function returned to normal over the next 3 weeks. He continues his multidrug therapy of leprosy without rifampicin.