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Lyme disease is recognized as the most common vector-borne disease in the United States. Surveillance data indicate both increasing numbers of Lyme disease cases and geographic expansion of areas where the causative spirochete, Borrelia burgdorferi, can be found. With prompt diagnosis and appropriate treatment in the acute stage, most patients will recover fully. Without treatment, however, the infecting pathogen remains within the body, often producing long-term complications, including musculoskeletal, neurologic, and cardiovascular effects. The authors describe early and late manifestations of Lyme disease, the appropriate use of diagnostic tests, the recommended treatment, and strategies for preventing tick-borne diseases nurses can share with patients.