Lyme borreliosis is a worldwide, multistage, and multi-system disease caused by borrelia spirochetes, which are transmitted by ixodes ticks. It is focally endemic in temperature climates of the northern hemisphere. Primary erythema migrans occurs at the site of inoculation. Secondary erythema migrans occurs at sites of hematogenous dissemination. Variations in genospecies account for variations in presentation, including borrelial lymphocytoma. Disseminated disease includes constitutional signs and symptoms, intermittent oligoarticular arthritis, meningitis, cranial neuritis, radiculoneuropathy, encephalopathy, atrioventricular block, and myopericarditis. Late persistent disease includes acrodermatitis chronica atrophicans, chronic arthritis, neurological impairment, and fatigue. There can be difficulties with both clinical and laboratory diagnosis. First-line oral therapies for early uncomplicated disease are doxycycline and amoxicillin. First-line intravenous therapy for complicated or resistant disease is ceftriaxone. Prevention includes avoiding tick habitats, dressing sensibly, judicious use of repellants, and early removal of imbedded ticks. Vaccination is indicated only for frequent or prolonged exposure to tick-infested habitat.