Bacterial enzymes have been isolated that catalyze the hydrolysis of organophosphate nerve agents with high-rate enhancements and broad substrate specificity. Mutant forms of these enzymes have been constructed through rational redesign of the active-site binding pockets and random mutagenesis to create protein variants that are optimized for the detoxification of agricultural insecticides and chemical warfare agents. In this review, the catalytic properties of two bacterial enzymes, phosphotriesterase and organophosphorus anhdrolase, are examined for their ability to hydrolyze organophosphate nerve agents.