Objective To investigate the effectiveness, safety and cost-effectiveness of leflunomide for rheumatoid arthritis, and formulate an evidence-based treatment plan for a patient with rheumatoid arthritis. Methods We searched the ACP Journal Club, The Cochrane Library (Issue 2, 2007) and MEDLINE (1990 to 2007), and critically appraised the available evidence. Results The available Level A (high quality) evidence showed that the efficacy and adverse events of leflunomide were comparable to those of methotrexate. The total cost of treating patients with leflunomide was significantly higher when compared to methotrexate. The combination of leflunomide and methotrexate in patients with active rheumatoid arthritis unresponsive to methotrexate monotherapy was less costly and more effective than the strategy excluding leflunomide. Given the current evidence, together with our clinical experience and the patient’s preference, methotrexate was administered to the patient. There was an inadequate response after 6 months of treatment. And then, adding leflunomide to methotrexate attained a remarkable response 3 months later. The patient is still being followed up. Conclusion treatment with leflunomide and methotrexate in RA patients can improve the clinical outcomes. Long-term efficacy and toxicity remain to be established.