<p>Cyber-Physical Systems (CPS) are integrated systems that consist of the computational and physical components with network communication to support operation in the physical world. My PhD dissertation focuses on the security and reliability of autonomous cyber-physical systems, such as self-driving cars, drones, and underwater robots, that are safety-critical systems based on the seamless integration of cyber and physical components. Autonomous CPS are becoming an integral part of our life. The market for autonomous driving systems is expected to be more than $65 billion by 2026. The security of such CPS is hence critical. Beyond traditional cyber-only computing systems, these complex and integrated CPS have unique characteristics. From the security perspective, they open unique research opportunities since they introduce additional attack vectors and post new challenges that existing cyber-oriented approaches cannot address well. <em>The goal of my research is to build secure and reliable autonomous CPS by bridging the gap between the cyber and physical domains.</em> To this end, my work focuses on fundamental research questions associated with cyber-physical attack and defense, vulnerability discovery and elimination, and post-attack investigation. My approach to solving the problems involves various techniques and interdis- ciplinary knowledge, including program analysis, search-based software engineering, control theory, robotics, and AI/machine learning.</p>