Computed tomography (CT) has had a profound effect on the practice of medicine. Both the spectrum of clinical applications and the role that CT has played in enhancing the depth of our understanding of disease have been profound. Although almost 90 000 articles on CT have been published in peer-reviewed journals over the past 40 years, fewer than 5% of these have been published in Radiology. Nevertheless, these almost 4000 articles have provided a basis for many important medical advances. By enabling a deepened understanding of anatomy, physiology, and pathology, CT has facilitated key advances in the detection and management of disease. This article celebrates this breadth of scientific discovery and development by examining the impact that CT has had on the diagnosis, characterization, and management of a sampling of major health challenges, including stroke, vascular diseases, cancer, trauma, acute abdominal pain, and diffuse lung diseases, as related to key technical advances in CT and manifested in Radiology.