This study covers the critical concerns related to the sizing, selection, installation, maintenance, and testing of pressure safety valves (PSVs). The aim is to ensure the safety of pressurized systems, hydrostatic transmission systems, and hydraulic plants, including process plants, thermal power plants, and nuclear reactor systems. PSVs are devices that ensure the safety and reliability of pressurized vessels, lines, and systems during overpressure events. The task of selecting which PSV features are of greatest value for a specific purpose is made complex—especially in the design of a high-pressure experimental thermal-hydraulic facility for hydrostatic and transient testing of the reactor system—when the systems are in the design and development phases and require qualification and demonstration to prove that they have reached a given level of technology readiness. The present study systematically and innovatively highlights the various complications related to this task, making it easy for users to follow the associated rules, guidelines, and recommendations. As a part of this research, case studies are presented to help readers better understand the applicable strategy and standards. A discussion and a review of PSV performance degradation and failure are summarized to afford a better understanding of such physics phenomena as cavitation and wear. This includes knowledge of root causes such as fluid-flow dynamics, boundary-layer formation and pressure drops, gas-bubble formation and collapse, geometric configurations, inlet/outlet piping, abrupt pressure fluctuations, and acoustic resonance. Moreover, this study discusses the servicing and testing of PSVs in a multiphase pressurized system. Overall, it provides a basic overview of how PSVs ensure the safety of pressurized systems, supported by both a real case study as well as actual industry practices.