Oxygen (O2) and Carbon Dioxide (CO2) are the two gases to be detected and controlled. Of interest might be a query of the evolutionary origin of each. From the cooling of the Big Bang (~13.8 Billion Years Ago [BYA]) came a quark-gluon plasma from which protons and neutrons emerged, producing H, He, Li. As H and He collapsed into the first stars at ~13.3 BYA carbon and monatomic oxygen were generated. Some 3 billion years ago greater amounts of diatomic oxygen (O2) were provided by earth’s photosynthesizing bacteria until earth’s atmosphere had sufficient amounts to sustain the life processes of multicellular animals, and finally higher vertebrates. Origin of CO2 is somewhat unclear, though it probably came from the erupting early volcanoes. Photosynthesis produced sugars with O2 a waste product. Animal life took sugars and O2 needed for life. Clearly, animal detection and control of each was critical. Many chapters involving great heroes describe phases involved in detecting each, both in the CNS and in peripheral detectors. The carotid body (CB) has played a crucial role in the detection of each. What reflex responses the stimulated CB generates, and the mechanisms as to how it does so have been a fascinating story over the last 1.5 centuries, but principally over the last 50 years. Explorations to detect these gases have proceeded from the organismal/system/ organ levels down to the sub-cell and genetic levels.