Probe molecules can be used to complement surface characterisation techniques for elucidating the nature of possible active sites in supported metal catalysts. 2,2-dimethylbutane (neohexane) is eminently suitable for this purpose because it combines an isobutyl and an ethyl group, representing two archetypes for hydrocarbon reactions on metal catalysts. In this review a survey is given of hydrogen-deuterium exchange, hydrogenolysis, and isomerization of 2,2-dimethylbutane mainly on Group 8-10 metals, copper, and rhenium, as well as on their various alloys. Hydrogen-deuterium exchange results are presented, and interpretations in terms of factors such as different surface morphologies are considered. For 2,2-dimethylbutane, hydrogenolysis is the main reaction on most catalysts. Isomerization is restricted to platinum, palladium, and to some extent to iridium and nickel. The relative importance of isomerisation versus hydrogenolysis has been examined and it is shown that this is critically dependent on a number of factors, such as the dispersion of the metal, alloy formation, non-metallic promoters, etc. The patterns of hydrogenolysis products can also be very informative because of the relationship between the observed product and the mode of adsorption of the 2,2-dimethylbutane molecule on different types of surface site. The use of 2,2-dimethylbutane to probe the surface composition of bimetallic particles has been discussed and the factors which influence the product distribution have been examined. The effect of non-metallic additives (water and chlorine) on the ratio of hydrogenolysis-to-isomerization is discussed and the possible important role of the metal-support interface (’adlineation sites’) is pointed out.