Tritium incorporation by synthetic and non-synthetic methods shares the common mechanism of labeling, requiring the activation of tritium gas. Activation can be by catalysts, hot tungsten wire, microwave discharge, etc. and results in the formation of tritium atoms and ions. The tritium atoms and ions may form free or sorbed onto a surface to react with substrate yielding different isotopomers and by-products. A third mechanism of labeling is tunneling. Tunneling is significant at near absolute zero temperature with liquid and solid tritium and is also significant when high pressures of tritium gas are used for labeling. Other parameters relating to supports, catalysts, purity of tritium gas, chemical nature of substrates, can also affect labeling. Tritium NMR spectroscopy can determine the tritium distribution in a molecule to aid in interpreting the labeling mechanism. The non-synthetic methods have the potential of labeling complex molecules of biomedical interest that are inaccessible by synthetic methods.