Leflunomide is a new isoxazole based disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. Leflunomide alone or combination with methotrexate has been reported to be safe as well as effective in patients with rheumatoid arthritis. Although a few cases of leflunomide-induced pancytopenia were identified, leflunomide-induced hemolytic anemia in rheumatoid arthritis has not been reported yet. We present a case of leflunomide-induced hemolytic anemia in a patient with rheumatoid arthritis.