Thanks to brain imaging great advances have been made concerning the comprehension of neural substrates related to panic disorder (PD). This article aims to: review the recent functional MRI (fMRI) studies concerning PD; correlate the PD fMRI neurobiological findings with the fear neurocircuitry hypothesis; discuss the fear neurocircuitry hypothesis and link it to cognitive-behavior therapy findings; and comment on fMRI study limitations and suggest methodological changes for future research. As a whole, there is increasing evidence that brain structures such as the prefrontal cortex, the anterior cingulate cortex and limbic areas (hippocampus and amygdala) might play a major role in the panic response.