We argue that the most ambitious science is intrinsically riskier science, more likely to fail. It is almost always a safer career strategy for the best scientists to seek to extend knowledge more modestly and to build incrementally on existing ideas and methods. Therefore, higher rewards for success are a necessary incentive to encourage top scientists to work on the most important scientific problems, ones where the solution has potentially revolutionary implications. We suggest that mega-cash prizes (measured in tens of millions of dollars) are a suitable reward for those individuals (or institutions) whose work has triggered radically new directions in science.