Lyme borreliosis is the most common tick-transmitted disease in the northern hemisphere and is caused by spirochaetes of the Borrelia burgdorferi species complex. A complete presentation of the disease is an extremely unusual observation in which a skin lesion results from a tick bite and is followed by heart and nervous system involvement, and later on by arthritis. Late involvement of eye, nervous system, joints, and skin can also occur. The only sign that enables a reliable clinical diagnosis of Lyme borreliosis is erythema migrans. Other features of some diagnostic value are earlobe lymphocytoma, meningoradiculoneuritis (Garin-Bujadoux-Bannwarth syndrome), and acrodermatitis chronica atrophicans. The many other symptoms and signs have little diagnostic value. Microbial or serological confirmation of borrelial infection is needed for all manifestations of the disease except for typical early skin lesions. However, even erythema migrans might not be pathognomonic for Lyme borreliosis, especially in the southern part of the USA where there is no microbiological evidence for infection with the agent. Treatment with antibiotics is beneficial for all stages of Lyme borreliosis, but is most successful early in the course of the illness. Prevention relies mainly on avoiding exposure to tick bites but there is some interest in chemoprophylaxis and also in vaccine development following initial disappointments.