The causative agent of Lyme disease, Borrelia burgdorferi, is a highly neurotropic organism that not only can produce symptomatic neurologic disease but also can exist dormant within the central nervous system (CNS) for long periods. Two distinct types of neuroborreliosis occur at different stages of Lyme disease. Second-stage Lyme meningitis resembles aseptic meningitis and is often associated with facial palsies, peripheral nerve involvement, and/or radiculopathies. Lyme meningitis may be the first evidence of Lyme disease, occurring without a history of erythema chronicum migrans or flu-like illness. Third-stage parenchymal involvement causes a multitude of nonspecific CNS manifestations that can be confused with conditions such as multiple sclerosis, brain tumor, and psychiatric derangements. Manifestations of CNS parenchymal involvement in Lyme disease are generally associated, however, with a history of erythema chronicum migrans, meningitis, or carditis. Both second- and third-stage Lyme neuroborrelioses are commonly misdiagnosed because they are relatively uncommon and because they mimic many better-known disorders.