Cyber-physical systems (CPSs) are ubiquitous, appearing in various domains such as transportation, energy, and healthcare. The seamless integration of computation, network communication, and control is fundamental for achieving goals that would otherwise be unattainable. Despite the significant benefits offered by this framework, safety and security remain critical challenges. Software rejuvenation (SR) provides an effective defense against cyberattacks by refreshing the runtime software that may have been compromised, restoring it to a clean state. This approach can be applied proactively by planning software refreshes in advance. While SR has proven effective in traditional computer systems, its application in CPSs presents additional complexities. The cyber-dynamics of a computer system evolve differently from the physical dynamics of a CPS, potentially undermining fundamental properties such as safety and liveness—i.e., the system’s ability to accomplish a specific task. In this chapter, we will demonstrate how to ensure safety and liveness in systems safeguarded by software rejuvenation.