The predatory imminence continuum (PIC) of antipredator defensive behavior has been a helpful strategy for modeling anxiety and fear-related disorders in nonclinical research. The PIC is divided into three different sequential stages that reflect defensive behavioral strategy in response to predatory imminence. However, the PIC was experimentally addressed with a series of shock-based fear conditioning experiments rather than predatory threats. In this article, we consider the PIC in a more naturalistic behavioral setting, focusing on analyzing the neural systems of animals responding to terrestrial and aerial predators. Of relevance, there is a sequential engagement of the distinct neural circuits along each phase of the PIC. In the preencounter phase, prefrontal cortical networks are particularly involved in planning and organizing behavioral responses to ambiguous threats. As the predatory cues or the real predator is detected, there is an engagement of amygdalar and hippocampal >
hypothalamic pathways in conjunction with the periaqueductal gray, which organize fear responses. This dynamic particularly reveals how specific neural circuits are set into action to subserve distinct defensive responses. Moreover, we further explore the neural circuits governing other fearful situations outside the context of the PIC, including agonistic social encounters and interoceptive challenges. This analysis reveals an interesting overlap between the neural systems responding to these threats and those involved in response to predatory threats. The present review clarifies how defensive circuits respond to natural threats and provides a more realistic view of the neural systems underlying anxiety and fear responses.