Molybdenum hydroxylases, which include aldehyde oxidase and xanthine oxidoreductase, are involved in the metabolism of some medicines in humans. They exhibit oxidase activity towards various heterocyclic compounds and aldehydes. The liver cytosol of various mammals also exhibits a significant reductase activity toward nitro, sulfoxide, N-oxide and other moieties, catalyzed by aldehyde oxidase. There is considerable variability of aldehyde oxidase activity in liver cytosol of mammals: humans show the highest activity, rats and mice show low activity, and dogs have no detectable activity. On the other hand, xanthine oxidoreductase activity is present widely among species. Interindividual variation of aldehyde oxidase activity is present in humans. Drug-drug interactions associated with aldehyde oxidase and xanthine oxidoreductase are of potential clinical significance. Drug metabolizing ability of molybdenum hydroxylases and the variation of the activity are described in this review.