Innovation is critical for both individual and evolutionary success, but creative disruption requires taking risks. NeuroEconomics is a new field that combines economic theories with cuttingedge neuroscience techniques to learn about the biological processes that motivate us to take risks and create new solutions to unforeseen challenges. In this lecture, Michael Platt describes how the brain overcomes uncertainty to explore novel alternatives and create new knowledge. Parallel findings from humans, monkeys, rodents, and worms indicate that a common suite of underlying mechanisms has evolved to control the desire to explore.