Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi and transmitted by ticks in the northern hemisphere. The disease is common in children. In addition to frequently recognized manifestations such as erythema migrans, neuroborreliosis, and Lyme arthritis, rarer manifestations, including eye and ear disease, are increasingly understood. Clinical diagnosis is supported by serologic confirmation. Improvement of laboratory methodology, especially polymerase chain reaction-based tests, is continuing. Actual treatment recommendations based on controlled studies reflect expanding scientific knowledge. In the United States, license of a vaccine to prevent infection in children is awaited. Lyme borreliosis is an intriguing human example of bacterial persistence in the presence of the host immune system. Chronic Lyme arthritis is a model of chronic arthritis resembling forms of arthritis of unknown cause, such as rheumatoid arthritis and juvenile idiopathic arthritis.