This chapter tackles the issue of Serious Games (SGs) curriculum integration approached from different perspectives (different levels, subject areas, instructional contexts, pedagogies, views, and visions over what it is already in practice and what is yet to be implemented). In light of the title of this book, it refers to Game-Enhanced Learning and not simply to game-based learning, thus supporting the concept that games can really contribute to improving and enhancing both collaborative and individual learning processes. The chapter is meant to trigger reflections on the potential of Serious Games in the present learning/teaching panorama and to explore how SGs can be considered suitable tools for sustaining the development of some relevant skills required to live and be proactive actors in the Knowledge Society, namely the so-called 21st Century Skills. Further, key challenges in the field of game-enhanced learning, with particular regard to pedagogical aspects are also in-depth explored by emphasizing the important role of teachers as to the choice of the SGs, their deployment, and the overall conduction of learning experiences.