Before the first description of Lyme arthritis in 1976, patients with this disease were often thought to have juvenile or adult rheumatoid arthritis. It is now known that Lyme arthritis is caused by a tick-borne spirochete that disseminates to joints, where it induces marked pro-inflammatory responses. In most patients, the arthritis resolves with antibiotic treatment. However, in the United States, about 10% of patients with Lyme arthritis develop persistent synovitis, which lasts for months or even several years after the apparent eradication of the spirochete from the joint with antibiotic therapy. The elucidation of Lyme arthritis, from acute infection to chronic synovitis, might help in our understanding not only of this entity, but also of other forms of chronic inflammatory arthritis, including rheumatoid arthritis.