ABSTRACT (full document on the ILADS website, Position Papers section) Background and Objective: The history of Lyme disease has been characterized by intense controversy over the diagnosis and treatment of this spirochetal infection. A recent high-profile article by Klempner et al.  focused attention on the optimal antibiotic treatment for chronic Lyme disease. Because this research study has generated significant conflict and confusion in the medical community, we undertook a critical analysis of its methodology and conclusions. Methods: The International Lyme and Associated Diseases Society (ILADS) reviewed the article according to established standards of evidence-based medicine. Study design and scientific objectivity were analyzed in light of peer-reviewed medical literature on chronic Lyme disease and associated tickborne illnesses. Results: Numerous methodologic weaknesses are noteworthy in the study. These include inappropriate study design with respect to the antibiotic treatment regimen; inappropriate selection and inadequate randomization of study patients; failure to explain positive cerebrospinal fluid findings, and failure to report objective neurocognitive assessments; failure to assess coinfection status of study participants; exclusion of pertinent findings from the final report, with inadequate follow-up of study participants; and failure to recognize that spirochetal infection cannot be excluded without adequate culture techniques. Conclusions: The study by Klempner et al. contains a series of interrelated errors. It fails to achieve its stated goal of being a long-term, properly randomized, placebo-controlled treatment trial. The study appears to be scientifically invalid and risks harming patients if its flawed conclusions are accepted uncritically by physicians. In view of the uninterpretable results of this study, further research into the use of long-term antibiotic therapy for chronic Lyme disease is warranted.