Lyme disease is the most common tick-borne disease in the United States and Europe. Increased awareness of the clinical manifestations of the disease is needed to improve detection and treatment. In the acute and late stages, Lyme disease may be difficult to distinguish from other disease processes. The epidemiology and pathophysiology of Lyme disease are directly related to the Borrelia burgdorferi spirochete and its effects on the integumentary, neurologic, cardiac, and musculoskeletal systems. Lyme arthritis is a common clinical manifestation of Lyme disease and should be considered in the evaluation of patients with monoarticular or pauciarticular joint complaints in a geographic area in which Lyme disease is endemic. Management of Lyme arthritis involves eradication of the spirochete with antibiotics. Generally, the prognosis is excellent. Arthroscopic synovectomy is reserved for refractory cases that do not respond to antibiotics.