Accurately estimating safety is critical to pursuing non-defensive survival behaviors, including reproduction and feeding. Relatively little attention, however, has been paid to how the human brain computes safety. We conceptualize a model that consists of two components: threat-oriented evaluations that focus on threat value, imminence, and predictability, while self-oriented evaluations focus on the agent’s experience, strategies, and ability to control the situation. Our model points to the dynamic interaction between these two components as a mechanism of safety estimation. Based on a growing body of human literature, we hypothesize distinct regions of the ventromedial prefrontal cortex respond to threat and safety. We suggest safety is not the inverse of danger, but reflects independent computations that mediate defensive circuits and behaviors.