As science becomes increasingly computational, the limits of what iscomputationally tractable become a barrier to scientific progress. Manyscientific problems, however, are amenable to human problem solving skillsthat complement computational power. By leveraging these skills on a largerscale---beyond the relatively few individuals currently engaged inscientific inquiry---there is the potential for new scientific discoveries.This book presents a framework for mapping open scientific problems intovideo games. The game framework combines computational power with humanproblem solving and creativity to work toward solving scientific problemsthat neither computers nor humans could previously solve alone. To maximizethe potential contributors to scientific discovery, the framework designs agame to be played by people with no formal scientific background andincentivizes long-term engagement with a myriad of collaborative orcompetitive reward structures. The framework allows for the continualcoevolution of the players and the game to each other: as players gainexpertise through gameplay, the game changes to become a better tool.The framework is validated by being applied to proteomics problems with thevideo game Foldit. Foldit players have contributed to novel discoveries inprotein structure prediction, protein design, and protein structurerefinement algorithms. The coevolution of human problem solving and computertools in an incentivized game framework is an exciting new scientificpathway that can lead to discoveries currently unreachable by other methods.