The aldo-keto reductase (AKR) superfamily comprises enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism, and detoxification. Substrates of AKRs include glucose, steroids, glycosylation end-products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (beta/alpha)(8) barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics.