Carbon dioxide has been monitored in the body using a variety of technologies with a multitude of applications. The monitoring of this common physiologic variable in medicine is an illustrative example of the different levels of evidence that are required before any new health technology should establish itself in clinical practice. End-tidal capnography and sublingual capnometry are two examples of carbon dioxide monitoring that require very different levels of evidence before being disseminated widely. The former deserves its status as a basic standard based on observational data. The latter should be considered investigational until prospective controlled data supporting its use become available. Other applications of carbon dioxide monitoring are also discussed.