We are living in the time of the digital revolution in which the world we know changes beyond recognition every decade. The positive aspect is that these changes also drive the progress in quality and availability of digital assets crucial for our societies. To name a few examples, these are broadly available communication channels allowing quick exchange of knowledge over long distances, systems controlling automatic share and distribution of renewable energy in international power grid networks, easily accessible applications for early disease detection enabling self-examination without burdening the health service, or governmental systems assisting citizens to settle official matters without leaving their homes. Unfortunately, however, digitalization also opens opportunities for malicious actors to threaten our societies if they gain control over these assets after successfully exploiting vulnerabilities in the complex computing systems building them. Protecting these systems, which are called high-assurance security systems, is therefore of utmost importance. For decades, humanity has struggled to find methods to protect high-assurance security systems. The advancements in the computing systems security domain led to the popularization of hardware-assisted security techniques, nowadays available in commodity computers, that opened perspectives for building more sophisticated defense mechanisms at lower costs. However, none of these techniques is a silver bullet. Each one targets particular use cases, suffers from limitations, and is vulnerable to specific attacks. I argue that some of these techniques are synergistic and help overcome limitations and mitigate specific attacks when used together. My reasoning is supported by regulations that legally bind high-assurance security systems' owners to provide strong security guarantees. These requirements can be fulfilled with the help of diverse technologies that have been standardized in the last years. In this thesis, I introduce new techniques for hardening high-assurance security systems that execute in remote execution environments, such as public and hybrid clouds. I implemented these techniques as part of a framework that provides technical assurance that high-assurance security systems execute in a specific data center, on top of a trustworthy operating system, in a virtual machine controlled by a trustworthy hypervisor or in strong isolation from other software. I demonstrated the practicality of my approach by leveraging the framework to harden real-world applications, such as machine learning applications in the eHealth domain. The evaluation shows that the framework is practical. It induces low performance overhead (