The evolutionary approach to human anxiety is based on the defensive responses that nonhuman animals show to fear-provoking stimuli. Studies performed mostly on rodents have related areas such as the medial prefrontal cortex, amygdaloid and hypothalamic nuclei, hipoccampal formation, and midbrain central gray to these responses. It is clear, however, that animals show different and sometimes opposite responses according to the threatening stimulus. These responses include immediate reactions such as freezing or flight, behavioral inhibition or avoidance, which are organized by at least partially distinct brain systems. As discussed in this chapter, several pieces of evidence indicate that these brain systems are similar in rodents and primates. In addition, recent neuroimaging studies also suggest dysfunctions in these systems are probably related to anxiety disorders in humans.