Panic disorder with agoraphobia (PD/AG) is one of the most costly and disabling anxiety disorders with a large range of secondary mental health problems. According to numerous clinical trials, cognitive-behavioural therapy (CBT) represents the most effective psychotherapeutic intervention for PD/AG. Little is known about the exact mechanisms of CBT and their neurobiological effects on the fear network. Within the PANIC-NET a unique, large multilevel and multicenter research project was implemented. By carrying out a randomized controlled clinical trial, different CBT components (exposure vs. cognitive techniques) were investigated in 360 patients in order to identify the core active ingredients of CBT. Furthermore, experimental add-on therapy with D-Cycloserine was tested. In an integrated approach, fear-circuit mechanisms were investigated employing psychophysiological techniques, functional neuro-imaging using 3T-fMRI and molecular genetic approaches.