Tick-borne relapsing fever is characterized by recurring fevers separated by afebrile periods and is accompanied by nonspecific constitutional symptoms. It occurs after a patient has been bitten by a tick infected with a Borrelia spirochete. The diagnosis of tick-borne relapsing fever requires an accurate characterization of the fever and a thorough medical, social, and travel history of the patient. Findings on physical examination are variable; abdominal pain, vomiting, and altered sensorium are the most common symptoms. Laboratory confirmation of tick-borne relapsing fever is made by detection of spirochetes in thin or thick blood smears obtained during a febrile episode. Treatment with a tetracycline or macrolide antibiotic is effective, and antibiotic resistance is rare. Patients treated for tick-borne relapsing fever should be monitored closely for Jarisch-Herxheimer reactions. Fatalities from tick-borne relapsing fever are rare in treated patients, as are subsequent Jarisch-Herxheimer reactions. Persons in endemic regions should avoid rodent- and tick-infested areas and use insect repellents and protective clothing to prevent tick bites.