AbstractDuring the last decade, models have been developed to characterize cellular metabolism at the level of an entire metabolic network. The main concept that underlies whole‐network metabolic modeling is the identification and mathematical definition of constraints. Here, we review large‐scale metabolic network modeling, in particular, stoichiometric‐ and constraint‐based approaches. Although many such models have been reconstructed, few networks have been extensively validated and tested experimentally, and we focus on these. We describe how metabolic networks can be represented using stoichiometric matrices and well‐defined constraints on metabolic fluxes. We then discuss relatively successful approaches, including flux balance analysis (FBA), pathway analysis, and common extensions or modifications to these approaches. Finally, we describe techniques for integrating these approaches with models of other biological processes Copyright © 2009 John Wiley & Sons, Inc.This article is categorized under: Models of Systems Properties and Processes > Cellular Models