Lyme disease is the most common vector-borne illness in North America, with the majority of cases occurring in the Northeast and upper Midwest. Lyme arthritis is the most prevalent manifestation of late-stage Lyme disease. Lyme arthritis typically presents as a monoarthritis or oligoarthritis in large joints such as the knee. Accompanying positive 2-tier Lyme serologies or polymerase chain reaction from synovial fluid/tissue is considered diagnostic for patients from an endemic area. The mainstay of initial treatment is a prolonged course of oral antibiotics.