Lyme disease is a multisystem inflammatory disease caused by infection with Borrelia burgdorferi. Soon after the tick bite which transmits the infection, the pathognomonic skin rash erythema chronicum migrans occurs in 50 to 70% of patients, often with associated symptoms resembling a 'summer cold' or viral infection. Therapy for this stage of disease consists of 3 to 4 weeks of oral therapy. The agents currently used are: amoxicillin (500 mg 3 or 4 times daily) with or without probenecid 500 mg 3 times daily, doxycycline (100 mg twice daily), or tetracycline (500 mg 4 times daily). Longer duration therapy has never been evaluated and therefore is not currently indicated. Even patients with severe early manifestations of Lyme disease should be treated orally. Later features of Lyme disease include carditis and neurological disease, which can occur days to approximately 9 months after the onset of illness, and arthritis and neurological disease which can occur weeks to years after the onset of the illness. Treatment at this stage is with 2 to 3 weeks of intravenous antibiotics, currently cefotaxime (3 g every 12 hours), ceftriaxone (1 g every 12 hours or 2 g every day) and benzylpenicillin (14 g in divided doses). There is no evidence that longer duration therapy is indicated or more efficacious. The exception to this suggestion is the patient with isolated facial seventh cranial nerve palsy; if such a patient has no other signs or symptoms to suggest Lyme disease and has normal spinal fluid, oral therapy is usually sufficient, although some physicians will give concomitant corticosteroids to hasten the resolution of the palsy. Of major consequence to the practitioner and patient is the possibility that persistent symptoms (e.g. fibromyalgia) may be caused by a process which is no longer antibiotic-sensitive. Special care in the management of so-called 'chronic Lyme disease' is crucial lest the clinician prescribes prolonged or unending courses of antibiotics for such noninfectious problems.