The goal of this chapter is to explore the generic organizational challenges faced by any high-risk organization and how they shape the social production of safety. Confronted with six generic categories of challenging dilemmas, high-risk organizations differ in their organizational responses, and in the mitigation strategies they put in place. However, this diversity does not mean that there is an infinite number of options. In the chapter, we introduce the concept of “safety regimes”, as a way to tackle the diverse ways in which companies operate, hence leaving aside the somewhat overused “safety culture” concept. The notion of “regime”, understood as a stable enough organizational equilibrium, offers an alternative way of documenting the organizational responses that high-risk organizations choose to develop and their direct or indirect consequences for the production of safety. The conditions for devoting such attention to the quality of organizing cannot be prescribed and decided upon once and for all. Rather than proposing top-down safety culture programs, and trying to make them fit into an ever-diverse and surprising reality on the ground, this chapter looks at another analytical option: clarifying the key dimensions that are fundamental to the establishment and comparison of safety regimes.