We appreciate all the kind remarks and suggestions from the many medical students over the past 3 years. Your positive reception has been an incredible encouragement, especially in light of the short life of the Case Files^® series. In this fifth edition of Case Files^®: Family Medicine, the basic format of the book has been retained. Improvements were made in updating many of the chapters. New cases include Substance Use Disorder, Asthma, Obstructive Sleep Apnea, Osteoporosis, and Opioid Use Disorder and Chronic Pain Management. We reviewed the clinical scenarios with the intent of improving them; however, their “real-life” presentations patterned after actual clinical experience were accurate and instructive. We had utilized focus groups of students to create a more user-friendly format for the digital platform such as bullet points for the case summary for faster reading and more plentiful use of subheadings throughout the text. We have used entrustable professional activities (EPA) corresponding to the learning objectives. The summary to the case scenarios are in bullet style to allow for easier reading. The multiple-choice questions (MCQs) have been carefully reviewed and rewritten to ensure that they comply with the National Board and the US Medical Licensing Examination format. Through this fifth edition, we hope that the reader will continue to enjoy learning diagnosis and management through the simulated clinical cases. It certainly is a privilege to be teachers for so many students, and it is with humility that we present this edition.