The efficacy of different therapeutic regimens for Lyme arthritis is reviewed. The first treatment for Lyme arthritis, intramuscular benzathine penicillin 2.4 million units weekly for 3 weeks, had a success rate of 35%. Another study employed intravenous penicillin G at a dosage of 20 million units daily for 10 days, which cured 55% of patients. Intravenous ceftriaxone has been shown to be superior to penicillin with a response rate of 94%. However, these results have been challenged in recent reports. Oral doxycycline or amoxicillin in association with probenecid seems to work equally well although neuroborreliosis was more frequent following treatment with amoxicillin. An anecdotal report indicates the usefullness of long-term benzathine penicillin for chronic Lyme arthritis. Long-term antibiotic therapy, which is recommended also for Reiter's syndrome, may be useful for eradicating the sanctuaries of Borrelia burgdorferi. Disease-modifying drugs such as hydroxychloroquine or sulphasalazine, a drug which is commonly used in reactive arthritis following enteric infections, may be of value in Lyme arthritis resistant to antibiotics but have not been tested to date. The role of intraarticular injections of steroids or synovectomy is still controversial. Antibiotic treatment is the cornerstone of Lyme arthritis treatment. Additional interventions should be studied for patients with Lyme arthritis resistant to antibiotics.