Lyme disease, the most common tick-borne illness in the United States, has an annual incidence of 0.5 percent in endemic areas. It most commonly occurs in the Northeast and upper Midwest, in areas that encourage and harbor the deer tick. The tick transmits an infection of the spirochete Borrelia burgdorferi that typically manifests as a localized skin lesion, erythema migrans. Rarely, Lyme disease manifests as localized arthritis, heart block or disease of the nervous system. Lyme disease is a clinical diagnosis, and laboratory tests should only be used to clarify diagnostic issues. The current standard for laboratory diagnosis includes a two-step approach using an initial immunoassay with a confirmatory Western blot. Treatment includes 10 to 21 days of oral doxycycline in nonpregnant adults or a similar course of amoxicillin in children or pregnant women. Overdiagnosis and overtreatment of Lyme disease have become common.