Panic disorder (PD) is a multidimensional anxiety disorder that involves the activation of a complex brain fear-network. The goals of this systematic review are to pinpoint some working functions of the most important neuroanatomical structures of fear and panic neurocircuitry and to raise hypotheses about how cognitive-behaviour therapy (CBT) may work on modulating the neurocircuitry of fear. The bibliographical search was carried out using mainly the PubMed database. Fifty-six articles were selected. A number of studies regarding several brain sites that participate in fear and anxiety circuitry were found and each region was described with its functionalities within the circuitry. Among the structures chosen were: the amygdala, the hippocampus and the prefrontal cortex, which play a special role. Study hypotheses showed that CBT may operate upstream from the amygdala and exert inhibitory effects on a variety of learned responses. It may work by strengthening the medial prefrontal cortex ability to inhibit firing of amygdala neurons, under the modulation of the hippocampus. Only two studies examined the modulation of fear neurocircuitry with CBT in PD. The results indicate that CBT has the potential to modify the dysfunctional neural circuitry associated with PD, but there is insufficient evidence to support the preliminary hypothesis.