The current chapter examines safety considerations related to hydrogen throughout the complete hydrogen energy value chain. The distinctive physicochemical characteristics of hydrogen that affects associated risks, such as elevated diffusivity, extensive flammability thresholds, minimal ignition energy, cryogenic properties, and hydrogen embrittlement, are analyzed. A review of historical hydrogen-related incidents is conducted to identify prevalent initiating events and primary failure mechanisms. The chapter examines the risks related to the storage, handling, and release of gaseous and liquid hydrogen. Methodologies for risk assessment, focusing on quantitative risk assessment and consequence analysis, are delineated. Mitigation measures, safety systems, and pertinent rules and standards are consolidated to facilitate the secure design and operation of hydrogen-based systems.