Biorepositories that collect, store, and distribute human and animal tissues and associated products including DNA, RNA, proteins, and other molecular components have important safety issues that must be considered, including but not limited to biological, chemical, physical, electrical, fire, and radiologic safety hazards. Every biorepository has its own unique set of safety issues and needs, which vary widely depending on the specific functions and goals of that specific biorepository. The United States and other countries, such as those in the European Union, provide regulations that address a wide variety of these general areas of safety. In addition, more local (e.g., city) or regional (e.g., state or province) regulations are often applied to many safety issues, particularly those involving physical, electrical, and fire safety. This chapter is intended to aid biorepositories in developing and maintaining a functional safety program. An important aspect of this consists of informing individuals involved in operating a biorepository about the sources from which they can obtain regulatory information. Although the chapter is focused on biorepositories, the discussions and precautions are applicable to other laboratories, especially those handling human and animal tissues and using chemicals. This chapter is not sufficient in and of itself to protect employees from all potential safety hazards, and laboratory safety continually evolves as more is learned about specific pathogens and how to prevent exposure to them. Thus, laboratories including biorepositories and their personnel must continually review and adjust their safety practices.