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<i>Objective</i>: Chronic Lyme disease has been a poorly defined term and often dismissed as a fictitious entity. In this paper, the International Lyme and Associated Diseases Society (ILADS) provides its evidence-based definition of chronic Lyme disease. <i>Definition</i>: ILADS defines chronic Lyme disease (CLD) as a multisystem illness with a wide range of symptoms and/or signs that are either continuously or intermittently present for a minimum of six months. The illness is the result of an active and ongoing infection by any of several pathogenic members of the <i>Borrelia burgdorferi sensu lato</i> complex (<i>Bbsl</i>). The infection has variable latency periods and signs and symptoms may wax, wane and migrate. CLD has two subcategories, CLD, untreated (CLD-U) and CLD, previously treated (CLD-PT). The latter requires that CLD manifestations persist or recur following treatment and are present continuously or in a relapsing/remitting pattern for a duration of six months or more. <i>Methods</i>: Systematic review of over 250 peer reviewed papers in the international literature to characterize the clinical spectrum of CLD-U and CLD-PT. <i>Conclusion</i>: This evidence-based definition of chronic Lyme disease clarifies the term's meaning and the literature review validates that chronic and ongoing <i>Bbsl</i> infections can result in chronic disease. Use of this CLD definition will promote a better understanding of the infection and facilitate future research of this infection.