The urea-retaining strategy of elasmobranchs has shaped their biochemistry and physiology; from their metabolic organization to the structure of their membranes. It has also affected their capacity to live in freshwater. Although much new information has been uncovered in the past 30years, many unanswered questions remain. These include: a) why was urea selected as the major organic osmolyte, b) why is glutamine used as a nitrogen donor, c) why was plasma albumin lost in marine elasmobranchs, d) what membranes are involved in urea retention in the gills, e) how do urea and trimethylamine N-oxide (TMAO) affect membranes, and f) why retain urea in freshwater. Hypotheses are presented for future investigations but some questions may require a time machine to answer.