This paper summarizes the thermodynamic theory of multi-electron transfer reactions and its implications for electrocatalysis. We discuss the fundamental differences between catalyzing reactions involving the transfer of one electron or no catalytic intermediates, two electron transfers with one catalytic intermediate, two electron transfer with two catalytic intermediates, and more than two electron transfers with more than one intermediate. These different classes of reactions imply different optimization problems for finding the best catalyst, dictated primarily by the thermodynamics of binding of the catalytic intermediates. The application of this theory to hydrogen evolution and oxidation, oxygen evolution and reduction, and carbon dioxide reduction, is discussed. (C) 2010 Elsevier B.V. All rights reserved.