The essential roles of proteins of the serpin family in many physiological processes, along with new discoveries of their unique folding properties, have attracted intense interest in recent years. Many serpins display unusual mobile behavior attributed to rearrangements of alpha-helical or beta-sheet domains, whereby large scale transitions accompany a variety of functions, including inactivation. This unusual behavior was first recognized with the X-ray structure of modified alpha 1-proteinase inhibitor. Subsequent experiments, including new X-ray structures, have revealed a surprising variety of conformations which are functionally important but only partially understood. We review here experimental evidence for conformations relevant to the serpin inhibitory mechanism.