Oxalate degrading enzymes have a number of potential applications, including medical diagnosis and treatments for hyperoxaluria and other oxalate-related diseases, the production of transgenic plants for human consumption, and bioremediation of the environment. This review seeks to provide a brief overview of current knowledge regarding the major classes of enzymes and related proteins that are employed in plants, fungi, and bacteria to convert oxalate into CO(2) and/or formate. Not only do these enzymes employ intriguing chemical strategies for cleaving the chemically unreactive C-C bond in oxalate, but they also offer the prospect of providing new insights into the molecular processes that underpin the evolution of biological catalysts.