Aldehyde reductase (ALR1, EC 1.1.1.2) and aldose reductase (ALR2, EC 1.1.1.21) catalyze the NADPH-dependent reduction of a wide range of aromatic and aliphatic aldehydes to their corresponding alcohols. Despite a recently expressed opinion that aldose reductase is of little consequence (Harding, 1992) the past few years have seen a great advancement in our knowledge of the structure and mechanism of both enzymes, and of aldose reductase in particular. The three-dimensional structure of pig (Rondeau et al., 1992) and human (Wilson et al., 1992) aldose reductase revealed that as an oxido-reductase the enzyme is unique in that it has a β/α-TIM barrel structure and is the first oxido-reductase known to possess such a structure and to not have a dinucleotide or Rossmann binding fold. Kinetic studies have shown that the enzyme operates by an ordered mechanism with NADPH binding first (Grimshaw et al, 1990; Kubiseski et al., 1992). The binding of coenzyme is very tight (≪lμM, see Grimshaw and Lai in this Proceedings) and following coenzyme binding there is a conformational change in the enzyme. This has been shown by fluorescence spectroscopy (Kubiseski et al., 1992); by a combination of chemical modification and X-ray crystallography (Kubiseski et al., 1994) and from a comparison of the three-dimensional structures of human and porcine aldehyde and aldose reductase (El-Kabbani et al., 1994). Structural studies have also revealed that an aldose reductase inhibitor (ARI), zopolrestat, binds in the active site (Wilson et al., 1993) and not at a site removed from the active site as suggested by the fact that all ARIs are uncompetitive or non-competitive inhibitors in the forward direction of the reaction (Sato & Kador, 1990). Most ARIs are in fact competitive with the alcohol product and binding of ARIs at the active site is, of course, feasible and understandable (Sato & Kador, 1990).