The treatment of glabellar frown lines with botulinum toxin injection is one of the most prevalent procedures in esthetic medicine. It is possible that the popularity of this intervention is not only owing to its cosmetic effect but also to modulatory effects on mood and affectivity. Recently, a series of studies including three randomized controlled trials have consistently shown that such effects can be used in the treatment of depression. Predominantly female patients suffering from partly chronic and treatment resistant unipolar depression experienced a quick, strong and sustained improvement in depressive symptoms after a single glabellar treatment with botulinum toxin A as a sole or adjunctive therapy. If these findings are further corroborated in additional studies, the ever-growing spectrum of applications for botulinum toxin may spread into the field of psychiatry, showing that the superficial paralysis of facial muscles may, probably via proprioceptive feedback mechanisms, have profound effects on the emotional brain.