It is not well understood why some patients develop a subjective syndrome that includes considerable fatigue, musculoskeletal aches, and neurocognitive dysfunction after receiving standard antibiotic courses for the treatment of Lyme disease. Some practitioners use the term "chronic Lyme disease" and order prolonged courses of oral and parenteral antibiotics, believing that persistent infection with Borrelia burgdorferi is responsible. However, well-performed prospective studies have found neither evidence of chronic infection nor a benefit worthy of long-term antibiotic therapy for these patients. Such extended antibiotic therapy poses hazards and cannot be viewed as acceptable. The term "chronic Lyme disease" should be discarded as misleading; rather, the term "post-Lyme disease syndrome" better reflects the postinfectious nature of this condition. Further research is necessary to understand possible mechanisms of these chronic symptoms following Lyme disease as well as to find effective therapies.