Atypical facial pain is a condition, which creates a difficult challenge for every physician, either for diagnosis or for choice of treatment. There are very few controlled studies and evidence-based data about what constitutes the gold standard treatment. Most physicians treat this condition with antidepressant agents, thinking that the psychiatric aspects, often present in these patients, play a fundamental role in the pathogenesis of the condition. However, antidepressant drugs are effective also in non-psychiatric patients, and new compounds, with no effect on psychological aspects, have recently seemed to show good activity in controlling pain in this disorder. We review the different possibilities available for treating this frustrating condition.