Lyme disease is a multisystemic disease caused by a spirochete, Borrelia Burgdorferi that is transmitted by ticks. A clinical diagnosis is easy when a tick bite is followed 3 weeks later by erythema migrans, than by involvement of nervous system, joints or heart. In case of neuroborreliosis, serological tests, performed in blood and cerebro-spinal fluid, support the diagnosis and patients recover rapidly with antibacterial treatments. However an accurate diagnosis remains sometimes problematic, especially distinction between a coincidental positive serologic test and a nervous system Lyme borreliosis which require antibiotics. Furthermore, the role of autoimmunity in the pathophysiology of late Lyme disease, antibiotic choice in early disease, duration of treatment, and utility of vaccination are discussed.