Now, 50 years since Linus Pauling described the molecular basis of sickle cell anemia, our understanding of human disease process and diagnosis has been profoundly advanced. With the entire sequence of the human genome in hand, the pace of discovery relating genetic change to human disease has never been more rapid. James and Margaret Thompson recognized the importance of initial discoveries in molecular genetics and, as visionaries of their time, sought to apply them directly to clinical medicine. In 1966, the Thompsons wrote a text specifically designed for medical school curriculums, providing a basis for the clinical application of recent genetic discoveries. The architecture of their original text is now in its sixth edition, and Nussbaum, McInnes, and Willard have done an excellent job at bringing medical students, residents, and primary care physicians up to date with this rapidly changing field.