This chapter offers a historic perspective of game science, starting with the launch of functionally integrated business games, and the mathematical theory of games during the 1950s. Since that time, gaming: the use of games in research and professional practice, has successfully evolved in many fields of application. During the 1960s, we are witnessing a broad proliferation of gaming approaches. They set the stage for the birth of various gaming associations. During the 1970s, those involved in gaming and simulation were searching for a common methodology that would enhance coping with the complexity of social and environmental issues. Three concepts guided that search. Dick Duke argued in his book Gaming: The Future Language that gaming is a language [Duke (Gaming: the future’s languge. Sage, 1974)]. Cathy Greenblat linked gaming with the notion of multiple realities [Greenblat (Principles and practices of gaming-simulation. Sage, 1981b)]. During the 1970s, based on System Dynamics, I was involved in the methodology of multi-actor, multilevel simulation and its linkages with game science in dealing with complexity and uncertainty of social systems [Klabbers et al. (Simulation & Games 11(1):59–86, 1980)]. These efforts had in common: developing a body of knowledge to form a cohesive structure of game science. They guided the current understanding that game science is most suitable to express and communicate complex multiple realities, which are interactive and dynamic. These notions require a more fundamental frame of reference than a narrowly instrumental approach. Game science connects three levels of inquiry: the philosophy of science level, the science level, and the application level. Combined, they enable researchers and practitioners to cope with epistemological and ethical systems-uncertainties, underpinning the transformative potentials of game science to change existing situations into more preferred ones, to envision and craft a better future.