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The aldo-keto reductase (AKR) superfamily consists of over 150 protein members sharing similar structure and enzymatic activities. To date, 13 human AKRs have been identified, and they participate in xenobiotic detoxification, biosynthesis and metabolism. Increasing evidence suggests the involvement of human AKR proteins in cancer development, progression and treatment. Some proteins demonstrate multiple functional features in addition to being a reductase for carbonyl groups. This review article discusses the most recent progress made in the study of humans AKRs.