In petroleum refineries, the concern for safety could be said to focus on two main areas: process safety and labor or personnel safety. These two areas are very different from each other, but both are important. They require two very different approaches to what one might call the safety problem. Process safety involves the development and implementation of interventions concentrated on preventing or minimizing the effects of loss of containment of flammable, toxic, or reactive chemicals. Labor or personnel safety interventions focus on the prevention or mitigation of hazards that can result in individual injuries or exposures; a much less catastrophic problem, but a no less important one. Through both approaches to the safety problem, we attempt to prevent or minimize the impact of accidents. There are many definitions for an accident, but for the purposes of this chapter, they will be considered unintentional events that result in undesirable consequences. Accidents occur in nearly every facet of our lives. Because in petroleum refineries, there is extensive heavy manual work (especially during maintenance turnarounds); there is large, heavy equipment; there are toxic, flammable and reactive chemicals; and there are high temperatures and pressures in many processes, it is no surprise that accidents occur here. Over the last 2030 years, in petroleum refineries and similar processes, there have been several significant watershed incidents that have fueled the development of many of the regulations and prevention activities that apply today and that serve to minimize the impact of the hazards typically associated with petroleum refining. The driving forces behind much of what makes up a modern safety and health program in the petroleum refinery in the United States are the regulatory agencies: the Occupational Safety and Health Administration (OSHA) and the U.S. Environmental Protection Agency (EPA). Although this chapter will draw heavily from these regulations, it will also include discussion on the ways and means that companies comply with these regulations (as well as other consensus standards and general good practice). The content of typical safety and health programs in petroleum refineries will also be covered, but the primary focus of this chapter will be on process safety, safe work practices or permit-to-work systems, and behavioral safety.