Although SSRIs are considered to be a first-line treatment for the most of anxiety disorders benzodiazepines are still widely used in clinical practice despite the risk of dependence and strong recommendation for their use as a second-line. Combination of the SSRIs and the benzodiazepines is widely used. Recently it has been suggested that the combination of SSRI and benzodiazepine is rational, because each drug has a different mechanism of action, the benzodiazepine enhancing GABAergic transmission, the SSRIs stimulating the 5-HT1A receptor that may inhibit the postsynaptic neuronal excitability in the amygdala and the prefrontal cortex that comprise the brain circuit of fear and anxiety. Recent Imaging studies suggested the hyperactivity of the amygdala in the patients with generalized social anxiety disorder and successful treatment with cognitive behavioral therapy or SSRI might significantly reduce the hyperactivity of the amygdala. It was suggested that the rational combination of SSRIs and benzodiazepines seems to be an effective and practical way of treatment for most anxiety disorders.