This volume constitutes the proceedings of the 5th International Conference on Serious Games, Interaction, and Simulation, held in Novedrate, Italy, in September 2015. The 16 revised full papers together with 2 keynote papers were carefully reviewed and selected for inclusion in this book. They focus on the design, development, use, and application of games for purposes other than entertainment. As such they cover areas like cognition, psychology, technology-enhanced education, evaluation and assessment, multimedia and information technology, and feature new scientific approaches and results from experiments and real-life applications.