The aim of this review was to analyze the current strategies of treatment and follow-up of disseminated and late Lyme borreliosis. A comprehensive search was performed using the Medline database. Only relevant reviews, expert guidelines and randomized controlled clinical trials were selected and, if necessary, open trials. Major drugs used in these studies were amoxicillin, doxycycline, penicillin G, and ceftriaxone. Oral administration of antibiotics was preferred in Lyme arthritis whereas parenteral drugs were mostly used in neuroborreliosis. The treatment duration usually ranged from 14 to 30 days. Prolonged antibiotic courses recommended by some authors in post-Lyme syndromes were not validated by several randomized placebo controlled studies. Follow up patterns were analyzed in order to determine possible prognosis parameters allowing to distinguih active Borrelia burgdorferi infection from a sequel of infection.