This book focuses on the predictive capabilities derived from digital representation of humans in simulation or virtual environments. It reports on models that facilitate prediction of safety and performance, and describes both innovative visualization techniques as well as the underlying mathematics and science. Contributions cover a wealth of topics, including simulation tools and platforms, virtual interactive design, model optimization methods, ontologies and knowledge-based decision support, human-computer interaction, human augmentation, and many others. The book gives special emphasis to cutting-edge simulation applications of human system modeling and optimization, including aviation, manufacturing and service industries, automotive design, product design, healthcare, sustainability, and emergency management. Based on the AHFE 2016 International Conference on Digital Human Modeling and Simulation, held on July 27-31, 2016, in Walt Disney World®, Florida, USA, it is intended as timely survey for researchers, engineers, designers, applied mathematicians and practitioners working in the field of Human Factors and Ergonomics.