Scientists, educators, and students benefit from having free and centralized access to the wealth of metabolic information that has been gathered over the decades. Curators of the MetaCyc database work to present this information in an easily understandable pathway-based framework. MetaCyc is used not only as an encyclopedic resource for metabolic information but also as a template for the pathway prediction software that generates pathway/genome databases for thousands of organisms with sequenced genomes (available at www.biocyc.org). Curators need to define pathway boundaries and classify pathways within a broader pathway ontology to maximize the utility of the pathways to both users and the pathway prediction software. These seemingly simple tasks pose several challenges. This review describes these challenges as well as the criteria that need to be considered, and the rules that have been developed by MetaCyc curators as they make decisions regarding the representation and classification of metabolic pathway information in MetaCyc. The functional consequences of these decisions in regard to pathway prediction in new species are also discussed.