Lyme borreliosis in humans is an inflammatory disease affecting multiple organ systems, including the nervous system, cardiovascular system, joints and muscles. The causative agent, the spirochaete Borrelia burgdorferi, is transmitted to the host by a tick bite. The pathogenesis of the disease in its early stages is associated largely with the presence of viable bacteria at the site of inflammation, whereas in the later stages of disease, autoimmune features seem to contribute significantly. In addition, it has been suggested that chronic persistence of B. burgdorferi in affected tissues is of pathogenic relevance. Long-term exposure of the host immune system to spirochaetes and/or borrelial compounds may induce chronic autoimmune disease. The study of bacterium–host interactions has revealed a variety of proinflammatory and also immunomodulatory–immunosuppressive features caused by the pathogen. Therapeutic strategies using antibiotics are generally successful, but chronic disease may require immunosuppressive treatment. Effective and safe vaccines using recombinant outer surface protein A have been developed, but have not been propagated because of fears that autoimmunity might be induced. Nevertheless, new insights into the modes of transmission of B. burgdorferi to the warm-blooded host have been generated by studying the action of these vaccines.