The 'detective' power of stable isotopes for processes that occurred in the past, and for elucidating mechanisms at the molecular level, has impressed researchers over the past 100 years, since the time when isotopes of elements were first discovered. While most are interested in the normalized abundance ratios of two isotopes of an element, further power was unleashed when researchers investigated the relationship of three or more isotopes of the same element, e.g. 16O, 17O, and 18O for oxygen. This Element focuses on the history of discovery of triple isotope effects, the conceptual framework behind these effects, and major lines of development in the past few years of triple oxygen isotope research.