Biorepositories containing human and some animal tissues have many potential safety issues, especially biohazards and chemical hazards. In addition, other safety issues include physical, electrical and other hazards. Rarely, radiological safety may be an issue. In general, the extent of specific safety issues depends upon the goals and operations of the biorepository. The United States of America (USA) as well as other countries such as those of the European Union (EU) have regulations that cover a broad range of safety issues such as protection of employees from bloodborne pathogens and chemical hazards. Frequently, safety issues involving physical, electrical and fire safety are local (e.g., city) or regional (state or province). The goal of this chapter is to aid biorepositories in developing and improving their safety programs. In part, this is approached by informing biorepository personnel of sources of regulatory information and aids in developing a general safety program. Of note, this discussion is not sufficient to protect employees from safety hazards or to ensure an organization has an adequate safety program. Laboratory safety is continually evolving as new issues in safety arise and new approaches to protect individuals and the organization develop. Therefore, personnel and organizations must constantly review their approaches to safety.