Cyber-physical systems (CPS) are emerging research areas that involve multiple disciplines. Two critical components in CPS are networking technologies and security. Because of the multi-disciplinary nature, the networking and security of CPS expand beyond traditional computing domains and have to consider the impact of applied physical systems. Therefore, new innovations are required such as novel transmission technologies, networking protocols, architectures, and security solutions. As a result, a significant amount of research work is expected for new models, performance analysis as well as evaluation, prototypes, and testbeds. This special issue focuses on research interests and activities related to networking and security in SmartGrid, Transportation and Medical Systems, with an emphasis on original analytical, experimental, and systems-related papers in these target domains. After a very careful review of the many highly qualified submissions, the editorial committee accepted a total of nine papers into this special issue. Among these, three papers are related to SmartGrid security, two relating to CPS security-driven wireless communication, three relating to CPS wireless backbone architectures and protocols, and one relating to medical system security. In SmartGrid security, Baumeister and Dong propose a security identity management solution for SmartGrid. Another work by Wen et al. designs a credit-based incentive tariff scheme. Yang, Chang, and Yu develop a solution to identify false data injection attack in power system. In security-driven CPS wireless communications, Si, Sun, and Zhang propose a solution to dynamically manage wireless spectrum based on quality of service and security to improve transportation CPS surveillance. The paper by An et al. integrates vulnerability into minimum cost-based wireless routing for sensor CPS. Kanjee and Liu propose a solution to relay-based authentication solution for medical systems. In wireless architectures and protocols, Yang et al. design a location-aware routing for vehicular CPS, Wang et al. develop a solution to collaborative measurement on network traffic that is friendly to transmission control protocol rate control protocols. Bhandare et al. evaluate the collision avoidance performance in wireless ad hoc backbone for CPS systems. On behalf of the editorial committee, we express our sincere thanks to all authors and reviewers for their significant contribution to this special issue. We are also grateful to Editors-in-Chief Drs. Chen Hsiao Hwa and Hamid R. Sharif and to the editorial staff for their excellent help and assistance. Without their contributions, it would have been impossible to produce this special issue. We hope that this special issue will inspire interested scholars to get involved in this promising and active research area.