The concept of evidence-based medicine has evolved over the past 2 decades, and has become a cornerstone to clinical decision-making in virtually every aspect of medicine. With a commitment to providing its members with high-quality evidence-based guidelines, the American Academy of Orthopaedic Surgeons has instituted concerted efforts since 2006 to develop clinical practice guidelines (CPGs) and appropriate use criteria (AUCs) for certain orthopaedic conditions. Many of these CPGs and AUCs detail the management of pediatric orthopaedic conditions. By the same token, members of the Pediatric Orthopaedic Society of North America (POSNA) Evidence Based Practice Committee have been publishing succinct evaluations of randomized controlled trials in pediatric orthopaedic surgery to create an evidence-based repository for quick reference to available high-level evidence as well as resource to identify gaps in the current research and identify opportunities for future investigation. In instances where higher-level evidence needed to develop CPGs is not available to address a critically important clinical question, consensus recommendations from experts in the field have been obtained to develop best practice guidelines (BPGs). The purpose of this review is to provide readers with a deeper understanding of the key principles of evidence-based medicine and methodologies used for the development of CPGs, AUCs, and BPGs.