AbstractHerein we briefly review theoretical contributions that have increased our understanding of the structure and function of metallo‐β‐lactamases and ureases. Both are bimetallic metalloenzymes, with the former containing two zinc ions and the latter containing two nickel ions. We describe the use of several different methodologies, including quantum chemical calculations, molecular dynamic simulations, as well as mixed QM/MM approaches and how they have impacted our understanding of the structure and function of metallo‐β‐lactamases and ureases. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1240–1262, 2006