Recent findings on the different functional properties of the neuroanatomical columnar subdivision of the Periaqueductal Gray (PAG) have provided a fundamental understanding for the pathophysiology of panic and anxiety disorder. In this review, we focus mainly on the prominent role of the PAG in defensive behaviour by combining both the behavioural and neuroanatomical data. We have applied the theoretical model of the "two dimensional defence system" by McNaughton and Corr (2004), and thereby constituted an organizational structure on the neuronal circuitry of the different brain regions in relation with this panic-and fearlike behaviour. It has become clear that the dorsal and lateral PAG are involved in the active emotional coping (fight and flight reaction), whereas the ventrolateral PAG is responsible for the passive emotional coping (quiescence/freezing). In this regard, the PAG and other related brain structures are working in concert with different neurotransmitters providing animals with defensive strategies in response to predatory threats. The functional roles of the PAG in these behaviours as characterized in animals warrants further translational studies in humans which may eventually lead to novel approaches in anxiety-and panic-related disorders.