Erythema migrans (EM) is the most common objective manifestation of Lyme disease, accounting for about 90% of cases. Establishing the diagnosis of EM is important because appropriate treatment with oral antibiotics at an early stage of infection with Borrelia burgdorferi results in excellent outcomes. This article includes a discussion of the epidemiology of EM and its clinical, differential, and laboratory diagnosis. The treatment of EM and the prevention of Lyme disease are also discussed.