Chronic arthritis occurs in 10% of Lyme disease patients. A patient had chronic septic Lyme arthritis of the knee for seven years despite multiple antibiotic trials and multiple arthroscopic and open synovectomies. Spirochetes were documented in synovium and synovial fluid (SF). Polymerase chain reaction (PCR) analysis of the SF was consistent with Borrelia infection. Persistent infection should be excluded with silver stains and cultures in any patient with chronic monoarticular arthritis and a history of Lyme disease.