Lyme disease, infection with Borrelia burgdorferi, is a focally endemic tick-transmitted zoonosis. During the 3 decades since the responsible spirochete was identified, a series of misconceptions and misunderstandings have become widely prevalent, leading to frequent misdiagnosis and inappropriate treatment. Persistent misconceptions concern the reliability of available diagnostic tools, the signs and symptoms of nervous system involvement, the appropriate choice and duration of antimicrobial therapy, the curability of the infection, and the cause of symptoms that may persist in some patients after treatment. Concern about disparate perspectives led the Institute of Medicine to review the subject. In this article we review the principal misconceptions, discussing their origins and the best currently available scientific evidence related to each one.