Isotopic labeling is a technique for tracking the passage of a sample of substance through a system. The substance is 'labeled' by including unusual isotopes in its chemical composition. If these unusual isotopes are later detected in a certain part of the system, they must have come from the labeled substance.

In ordinary isotopic labeling, there are two ways to detect the presence of labeling isotopes. Since isotopes have different masses, they can be separated using mass spectrometry. Another consequence of the difference in mass is that molecules containing isotopes have different vibrational modes ; these can be detected by infrared spectroscopy.

A common variation on this procedure is radioisotopic labelling, in which the unusual isotopes are radioactive and detected by their radioactivity.

An example of the use of isotopic labeling is the study of phenol (C₆H₅OH) in water by replacing common hydrogen (protium) with deuterium. Upon adding phenol to deuterated water (water containing D₂O in addition to the usual H₂O), researchers observed the substitution of deuterium for the hydrogen in phenol's hydroxyl group (resulting in C₆H₅OD), indicating that phenol readily undergoes hydrogen-exchange reactions with water. Only the hydroxyl group was affected, indicating that the other 5 hydrogen atoms did not participate in these exchange reactions.