Treating glabellar frown lines with injections of botulinum toxin is the most frequently applied procedure in aesthetic medicine. In addition to its cosmetic effect, botulinum toxin may also positively modulate mood and affect, which may contribute to its popularity. A series of clinical studies has shown that this modulation can be used in the treatment of major depression. After a single glabellar treatment with botulinum toxin, patients suffering from unipolar depression experienced a quick, strong and sustained improvement in the symptoms of depression. Preliminary data suggest that botulinum toxin therapy may also be effective in the treatment of other mental disorders characterized by an excess of negative emotions, such as borderline personality disorder. Thus, the extreme bottom-up approach of paralyzing the facial muscles to influence the emotional brain via proprioceptive feedback mechanisms may represent a paradigm shift in psychiatric therapy.