The ISPE Good Practice Guide: Process Gases, Second Edition presents recent advances in construction materials and updates on current good practices. This edition is aligned with the latest regulatory guidance including EU Annex 1 (revised 2022), EU Annex 15, the FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice, and the FDA draft Guidance for Industry: Current Good Manufacturing Practice for Medical Gases. Additionally, content was revised based on the latest ISO, ASTM, and ASME standards, as well as the ISPE Good Practice Guide: Critical Utilities GMP Compliance and the ISPE Good Practice Guide: Good Engineering Practice. This Guide covers all aspects of pharmaceutical gas systems, including generation technologies and design options for control/monitoring and system operation, and sustainability requirements. General properties and characteristics of the atmospheric gases (nitrogen, oxygen, and argon), carbon dioxide, and compressed air are presented, along with pharmacopeia requirements. Criteria for determining whether a pharmaceutical gas is an excipient or process aid is included. This evaluation dictates the quality properties the gas must meet, informing system design options. The air compressor chapter discusses compressor types, traps, filters, contaminant reduction, installation and layout, and energy recycling options. In addition, system distribution considerations are presented, including designing for redundancy, piping options, and available system and filtration components. This Second Edition adopts the ISPE Baseline Guide: Commissioning & Qualification (Second Edition) integrated C&Q strategy to streamline the effort for process gas systems. System designers are encouraged to consider where the gas will be used and for what purpose when developing the user requirements for use points. New to this version is an overview of the global pharmacopeias and global regulations for medical and medicinal gases, added because of Annex 1 requirements. The Guide highlights the general differences and commonalities in the pharmacopeias and lists applicable technical standards.