Reaction mappings are of fundamental importance to researchers studying the mechanisms of chemical reactions and analyzing biochemical pathways. We have developed an automated method based on integer linear optimization, ILP, to identify optimal reaction mappings that minimize the number of bond changes. An alternate objective function is also proposed that minimizes the number of bond order changes. In contrast to previous approaches, our method produces mappings that respect stereochemistry. We also show how to locate multiple reaction mappings efficiently and determine which of those mappings correspond to distinct reaction mechanisms by automatically detecting molecular symmetries. We demonstrate our techniques through a number of computational studies on the GRI-Mech, KEGG LIGAND, and BioPath databases. The computational studies indicate that 99% of the 8078 reactions tested can be addressed within 1 CPU hour. The proposed framework has been incorporated into the Web tool DREAM ( http://selene.princeton.edu/dream/ ), which is freely available to the scientific community.