AbstractMultivalent systems are well known for their enhanced ability to bind multivalent counterparts. This contribution addresses the question whether they can also behave as cooperative catalysts. Analyzing examples from our own laboratory we show that self‐assembled systems obtained by covering gold nanoclusters with thiol‐terminated amino acids and peptides behave indeed as cooperative catalysts. By comparing their activity profiles with those of discrete, multivalent systems we show what are minimal conditions to elicit cooperativity in multivalent systems. Reactions taken into considerations for our analysis are the hydrolyses of carboxylate‐ and phosphate esters. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.