The term 17beta-hydroxysteroid dehydrogenase (17beta-HSD) describes an enzyme that stereospecifically reduces or oxidizes a keto- or hydroxy group at C17 of the steroid scaffold, respectively. Fourteen mammalian 17beta-HSDs have been identified so far and nine sequence homologs are found in zebrafish. 17beta-HSDs additionally active in fatty acid metabolism display high sequence conservation and widespread tissue expression. Homologs of these multifunctional 17beta-HSDs have been identified in flies, worms and yeast, and steroid-converting activity was demonstrated in some cases. The "classical" 17beta-HSDs, types 1, 2 and 3, are steroid-specific enzymes expressed in few tissues. They may have arisen at the beginning of vertebrate evolution allowing new, differently controlled modes of steroid hormone action. These findings reflect on two aspects: (1) the evolutionary origin of steroid-specific enzymes and (2) a possible conservation of steroid hormone function in invertebrates through currently unknown mechanisms.