Lyme disease is a multisystem disease that occurs in North America, Europe, and Asia; it is the most common tickborne disease in the United States and is endemic in several areas. The number of reported cases has increased steadily since 1982, when systematic national surveillance was initiated; the actual number of patients diagnosed with Lyme disease is thought to be much higher than the reported number. Most individuals diagnosed early with the characteristic rash, erythema migrans, respond well to short courses of oral antibiotics. In patients who present with later stages of illness, the diagnosis is based on clinical and epidemiological evidence of disease and is supported by serologic testing. Accurate diagnosis is possible through use of a two-tiered antibody test. The stage and organ system involved guide the selection of an antibiotic regimen. Untreated infection can spread to joints, the heart, and the nervous system. Personal protective measures are important for prevention of infection. Lyme disease is a national notifiable disease (voluntary); however, many states require mandatory surveillance and reporting.