This handbook provides a comprehensive and systematic introduction to the Cyber-Physical Systems (CPS) from the aspects of fundamental concepts, major challenges, and effective solutions. The focuses are on: infrastructure and design methodology, communication protocol, embedded systems, real-time CPS, time synchronization in CPS, CPS collaborative computing, reputational computing in CPSs. A comprehensive vision on the applications are also presented in the fields of smart Grid, software infrastructure for smart building monitoring, healthcare monitoring, safety & security in industrial process, structure monitoring, etc. This handbook is intended for a wide range of audience, including academic researchers, graduate students, practitioners in industry, and research engineers. It can be an excellent reference work for the academic researchers, industry practitioners, and research engineers working in the field of CPS to learn the state-of-the-art technologies.