This review imparts the history and the present status of the indicator dilution technique with quantitative bolus injection. The first report on flow measurement with this technique appeared 100 years ago. In 1928, the use of intravascular dyes made possible a widespread application in animals and human during the next decades. Multiple indicators, radioactive tracers, inlet–outlet detection and residue detection were introduced in the 1950s and 1960s, and refined along with the development of indicator kinetics. From the 1970s, a wide clinical use in the study of heart, brain, lungs, liver and kidneys developed, and powerful computers in the 1980s and 1990s accorded the technique a new dimension. Today, the indicator dilution technique, on one hand, is applied in the same way as 100 years ago, on the other hand it forms the basis of quantitative SPECT, positron emission tomography, and dynamic MR scans. The technique still undergoes refinement and elaboration as a lasting concept with a high potential for further development.