The purpose of this clinical practice guideline is to evaluate the current best evidence associated with treatment. Evidence-based medicine (EBM) standards advocate for use of empirical evidence by physicians in their clinical decision making. To assist with access to the large resources of information, a systematic review of the literature in publication between April 2010 and May 2012 has been conducted. It highlights where there is good evidence, where evidence is lacking, and what topics future research will need to target in order to help facilitate evidence-based decision making in the treatment of patients with osteoarthritis of the knee. AAOS staff methodologists assisted the physician/clinician work group in evaluating the existing literature so that they could formulate the following recommendations based on a rigorous systematic process.