Lyme borreliosis is a vector-borne zoonotic disease transmitted by ticks infected with spirochetal bacteria belonging to the genus Borrelia. Affected dogs typically present with intermittent, lameness, fever, inappetance, lethargy, and focal lymphadenopathy. Although infrequently reported, clinical manifestations in horses include neurologic abnormalities, uveitis, and cutaneous lymphoma. Diagnosis is based on a combination of history, clinical signs, laboratory findings, exclusion of other diseases, and response to treatment. Treatment consists of an extended (eg, 30-day) course of antibiotics, supportive measures including analgesia, and immunosuppressive therapy in the case of autoimmune reaction.