Genetic characterization has served as a plant genetic resource management tool almost from the inception of genebanks.  Its use has intensified during the last decade, due to the development of relatively inexpensive and high-throughput DNA analytical capabilities, and information management technologies which have evolved almost unimaginably.  The constituent genebanks of the U. S. National Plant Germplasm System (NPGS) have deployed these technologies and the information they generate to try to enhance the efficiency and effectiveness of plant genetic resource acquisition, maintenance, regeneration, evaluation, enhancement, information management, and distribution/customer service.  In doing so, the NPGS has faced complicated technological and institutional challenges—some of a general nature, and some specific to particular crops and/or crop research communities.  A review of the approaches employed and solutions obtained by the NPGS may enable germplasm users and genebank personnel to more effectively address these and similar challenges in the future.