Fundamental studies of the atomic elements in the first quarter of the 20th century resulted in the recognition of the isotopes of oxygen, carbon, nitrogen, and finally hydrogen. The unique character of a hydrogen isotope led quickly to its enrichment, to the investigation of its biologic effects, and ultimately to its use as a tracer in biologic transformations. As a tracer, deuterium provided a totally new appreciation of the living organism: as one in constant flux. Together with 15N, 13C, and 18O, the foundation of modern biochemistry was laid. The milestones in stable isotope history, their architects and their impact on the research of that time are reviewed.