An examination of the published literature is essential to understanding the growing spectrum of acute and chronic manifestations of Lyme disease. The all to common absence of a physical examination finding or a reliable test underlies the need for make a clinical diagnosis. The growing number of strains and species of Borrelia and other tick borne illness further complicates the need for reliable diagnostic tests. Our increasing understanding of pathophysiologic mechanisms further complicated finding an effective antibiotic regiment. ILADS published their evidence based treatment guideline in 2014 based on a GRADE assessment. A GRADE assessment of demonstrated the weakness of evidence for retreatment. The ILADS panel conclusion included that 1) guidelines should not constrain the treating clinician from exercising clinical judgment in the absence of strong and compelling evidence to the contrary, 2) recommendations take into account not only the quality of the evidence, but also the balance between benefits and harms and patient values and preferences, 3) patient-centered care focuses on achieving treatment outcomes that patients value, including the restoration of health, prevention of health deterioration and the provision of treatments that have the potential to improve quality of life, and 4) shared decision-making takes into account the best scientific evidence available, clinical expertise and the role of patient’s values and preferences in deciding among available treatment options. Specific recommendations will be highlighted.