Adaptation practice is a novel and dynamic field. This is reflected by an as yet limited experience in how climate change uncertainties can be best dealt with in particular situations. This chapter synthesises the theoretical (scientific) and practical aspects of the preceding chapters, draws key lessons and provides guidance for those involved in supporting and ultimately making adaptation decisions. For this purpose a Common Frame of Reference (i.e. common definitions, principles and understandings) for dealing with uncertainties in climate adaptation decision-making is presented and applied to the analysis of the twelve real-life cases presented in this book. This framework intends to support complex climate adaptation decision-making processes that have to deal with uncertainties and still make informed decisions. Two central questions were addressed and applied to the cases reported: (i) how did the approaches used to deal with climate uncertainty influence the adaptation decision-making process and (ii) have better informed adaptation decisions been made because uncertainties were conscientiously addressed? The objective of this chapter is not to provide a simple checklist to be followed when facing uncertainties in a climate adaptation process but rather to inform and guide the reader by presenting key lessons and insights from real-life cases where decision-makers and those that support them have already faced and responded to climate adaptation related uncertainty.