This chapter provides guidance for solving practical, high-level management and policy challenges in sustainability and disaster resilience. These two fields must be considered together so that they do not work at cross-purposes. Sustainability is framed in a positive and useful way that transcends shallow and self-serving treatments that are all too common. Although sustainability is a multi-faceted problem, climate change is the focus because it is globally important and because it is particularly troublesome due to its global and long-term scale. The discussion on sustainability highlights the challenge of extreme uncertainty. Knowledge of system complexity is necessary for understanding and contending with extreme uncertainty. Thus, this chapter summarizes some fundamental knowledge and draws from it recommendations for decision-making. An example illustrates the suggested approach and provides additional insight. Complex systems are hard to understand and no course of action is guaranteed to be successful. However, without systems thinking, failure is almost assured. The recommendations in this chapter, although not infallible, will help find effective ways to intervene in societal systems to meet stated objectives while avoiding unintended consequences.