Since its first discovery, CLU has been fascinating many researchers around the world, probably because CLU has always been a surprise. In many studies, CLU showed up unexpected as a secondary but significant observation in the hands of scientists which probably had no specific intention to study it. Too often the first descriptions of the structure, action, and biological meaning of CLU had to be changed in the light of novel and rather surprising findings, making what was thought to be well established, actually obsolete. CLU is a biological object still in movement. To understand more, we will have to cope correctly with this challenge. As an Ariadne's thread, following CLU we will challenge our static ideas pointing to alternative views which will possibly lead us to a different thinking and a much better understanding of the complexity of cell transformation. In this final chapter, we will provide “take home messages” from the chapters of vols. 104 and 105 concerning the most up to date knowledge about CLU. Then we will provide some agreements and consensus in this field, wherever possible. Highlighting possible faults or misunderstandings, we will define the open issues which will very likely drive the research on CLU in the near future. Finally, we will address how this novel knowledge about CLU may possibly result in important implementations, from basic science all the way to the clinical setting, in the fight against cancer.