1. Eugene D. Shapiro, MD* 1. *Departments of Pediatrics, Epidemiology of Microbial Diseases, and Investigative Medicine, Yale University Schools of Medicine and of Public Health and Graduate School of Arts and Sciences, New Haven, CT. * Abbreviations: DEET: : N,N-diethyl-meta-toluamide ELISA: : enzyme-linked immunosorbent assay EM: : erythema migrans STARI: : southern tick–associated rash illness 1. Although Lyme disease, caused by Borrelia burgdorferi , is the most common vector-borne disease in the United States, there is considerable misunderstanding about the clinical manifestations and consequences of this infection. (1)(2) 2. When to perform diagnostic tests and how to interpret the results for antibodies against B burgdorferi are common sources of confusion for physicians and patients. (3)(4)(5) 3. Misinformation about chronic Lyme disease on the Internet and in popular media has led to publicity and anxiety about Lyme disease that is out of proportion to the actual morbidity that it causes. (6)(7)(8) After completing this article, readers should be able to: 1. Understand the ecology and the epidemiology of Lyme disease. 2. Know when to order and how to interpret serologic tests for the diagnosis of Lyme disease. 3. Understand the clinical manifestations of Lyme disease and appropriate treatment Lyme disease is the most common vector-borne disease in the United States. In the United States, the spirochete Borrelia burgdorferi sensu stricto (hereafter termed B burgdorferi ) is the only pathogen that causes Lyme disease. However, in Europe and Asia, Borrelia afzelii , Borrelia garinii, and other related species, in addition to B burgdorferi , cause Lyme disease. In the United States, these bacteria are transmitted by hard-bodied ticks, including Ixodes scapularis (the black-legged tick, commonly called a deer …