We are delighted that the physiological community so eagerly welcomed the Second Edition of our book. The 3-fold philosophy that has guided us in the previous editions has endured as we prepared the Third Edition. First, we combine the expertise of several authors with the consistency of a single pen. In the First Edition, we achieved this singleness of pen by sitting—shoulder to shoulder—at a computer as we rewrote the primary copy of our authors, line by line. By the time we began editing the Third Edition, one of us had moved from New Haven to Cleveland. Even so, we continued to edit jointly and in real time— monitor to monitor—using desktop-sharing software. After more than two decades, we have become so accustomed to each other’s writing styles that we can literally finish each other’s sentences. Second, we still integrate physiological concepts from the level of DNA and epigenetics to the human body, and everything in between. Third, we complete the presentation of important physiological principles by pairing them with illustrations from pathophysiology, thereby putting physiology in a clinical context. In this Third Edition, we have updated the entire book to reflect new molecular insights. In the process, we have shortened the printed version of the book by 40 pages. The Third Edition contains 20 new or redrawn figures as well as enhancements to 125 others. Similarly, we included over 190 tables. In the First Edition, we launched the concept of online-only Notes—electronic footnotes that were available on the Student Consult website. These Notes (indicated by icons in the print version of the book) amplify concepts in the text, provide details and derivations of equations, add clinical illustrations, and include interesting facts (e.g., biographies of famous physiologists). With the increased use of online materials and eBooks, our readers may welcome our updating of the previous Notes as well as a 13% increase in the total number of Notes for the Third Edition, for a total of about 750.