Lyme disease is a multisystem disorder caused by a tick-transmitted spirochete, Borrelia burgdorferi. Clinical manifestations typically begin with characteristic skin lesions, erythema (chronicum) migrans. Weeks to months later, some patients develop the second stage of the illness characterized by neurologic abnormalities, migratory joint pain, cardiac involvement. Months to years later, in many patients the disease progresses to the third stage of manifestation such as chronic arthritis, chronic encephalomyelitis, acrodermatitis chronica atrophicans and keratitis. Zoonotic infection with B. burgdorferi is also widespread within endemic regions among domestic as well as wild animals. The diagnosis is based on clinical and epidemiological findings in most patients, particularly those with erythema migrans or tick bites. Detection of specific antibodies to B. burgdorferi is a useful confirmatory test in many patients. In atypical cases, a positive test result can be valuable for determining the diagnosis. However, serologic testing in Lyme disease is not yet standardized and the results obtained from different assay systems or commercial kits may vary. Moreover, because of poor agreement in sensitivity and/or specificity, data obtained from different laboratories are not comparable. We emphasize that serologic findings must be interpreted with caution; the physician must beware of its strengths and limitations.