Understanding enzyme function is exciting research because diverse and often unpredictable solutions are developed to perform seemingly impossible tasks. Enzymes are such powerful catalysts as they lower the height of the activation energy barrier. How do enzymes bring about this decrease in ΔG≠? Many excellent attempts to dissect this into discrete enthalpic and entropic factors have been made. Rate accelerations are favored when the enzyme specifically binds and assembles substrates at the active site and then provides an optimal arrangement of catalytic groups. This is clearly an entropic (ΔS≠) contribution. Stabilization of the transition state through enthalpic (ΔH≠) factors like select hydrogen bonds, salt links, acid–base groups, and covalent interactions is another feature. Various tricks that enzymes employ in achieving catalytic prowess are shown in Fig. 4.1. These components are best understood through case studies, and we will do this through representative examples for each.