Arthritis is one of the most prominent features of Lyme disease, the tick-borne illness caused by Borrelia burgdorferi. Although the pathogenesis of Lyme arthritis is complex and still under study, the clinical presentation and natural history have been established by long-term observation of untreated and treated patients. This review addresses the clinical presentation of Lyme arthritis as a mono- or oligoarticular relapsing/remitting arthritis primarily affecting the large joints and describes presentations in which arthralgias rather than arthritis are seen. Strategies for diagnosis and treatment are discussed, and methods are reviewed for addressing treatment-refractory Lyme arthritis and arthralgias that may occur after treatment of Lyme disease (sometimes as a component of what is known as the post-Lyme disease syndrome).