The document discusses challenges for autonomous response to unexpected situations in complex environments. It proposes using "pick-up games" as a way to test and develop technologies for autonomous systems to respond to such situations. The document outlines several potential challenges and projects for the US Air Force Research Laboratory (AFRL) to lead in developing theories, tools, and techniques to enable effective autonomous response in situations involving strike, electronic warfare, cyber operations and intelligence, surveillance and reconnaissance. These include developing formalisms for situational representation, verification of intelligent machines, uncertainty management, and rapid training transfer for autonomous systems.