There are two stereochemical classes of hydratase-dehydratase enzymes. Those that catalyze the addition of water to alpha,beta-unsaturated thioesters give syn addition-elimination stereochemistry, whereas those that catalyze the addition of water to conjugated carboxylate substrates give anti stereochemistry. This dichotomy could reflect different adaptive advantages or contingencies of separate evolutionary histories. Determination of the nonenzymatic stereochemistry of deuterium oxide addition to fumarate and to S-crotonyl N-acetylcysteamine has provided direct evidence for the importance of the contingencies of evolutionary history, rather than chemical efficiency, in the pathways of these hydratase-dehydratase enzymes.