This article reviews aspects of the literature on neuroscience, psychiatry, and cognitive and evolutionary psychology to illustrate how primitive brain mechanisms that evolved to assess environmental threats underlie psychiatric disorders, and how beliefs can affect psychiatric symptoms through these brain systems. Psychiatric theories are discussed that (a) link psychiatric disorders to threat assessment and (b) explain how the normal functioning of threat assessment systems can become pathological. Three brain structures that are consistently implicated in psychiatric symptomology also are involved in threat assessment and self-defense: the prefrontal cortex, the basal ganglia, and parts of the so-called limbic system. We propose that as these structures evolved over time they formed what we refer to as evolutionary threat assessment systems, which detect and assess potential threats of harm. Drawing on various psychological and psychiatric theories we propose how beliefs about the world can moderate psychiatric symptoms through their influence on evolutionary threat assessment systems.