Cortisol is synthesized by II beta-hydroxysteroid dehydrogenase type I, inhibitors of which may treat disease associated with excessive cortisol levels. The crystal structures of II beta-hydroxysteroid dehydrogenase type I that have been released may aid drug discovery. The crystal structures have been analyzed in terms of the interactions between the protein and the ligands. Despite a variety of structurally different inhibitors the crystal structures of the proteins are quite similar. However, the differences are significant for drug discovery. The crystal structures can be of use in drug discovery, but care needs to be taken when selecting structures for use in virtual screening and ligand docking.