Although the fields of dendrochronology and light stable-isotope mass spectrometry emerged at different times in the first half of the 20th Century, their convergence with the earliest measurements of isotope composition of tree rings is now ca. 70 years old. Much of the early stable isotope analysis (including on wood) explored natural variation of isotopes in the environment, but those researchers making the measurements were already contemplating the role of the isotope composition of the source substrates (e.g., water and CO2), biochemical fractionation, and environment as contributors to final tree-ring isotope values. Growing interest in tree-ring isotopes was heavily motivated by paleoclimate or paleoatmosphere reconstruction, but this new field rapidly developed to generate greatly improved mechanistic understanding along with expanded applications to physiology, ecology, pollution, and more. This chapter primarily charts the historical progression in tree-ring C-H-O isotope studies over those seven decades, but it also identifies potential productive emerging and future directions.