Treatment-resistant mood disorders pose a great socioeconomic and life-threatening burden on public health system. On one hand, major depressive disorder (MDD) has a lifetime prevalence of 17-21%, and it is a leading cause of disability adjusted life years worldwide accordingly to The Global Burden of Disease study. However, only 30-40% of patients achieve remission following a standard trial with a first-line antidepressant agent. On the other hand, bipolar disorder (BD) affects about 2% of the world’s population, with subthreshold forms affecting another 2%. It is known that non-response in bipolar depression is also highly prevalent, and it occurs in 40% of patients. Moreover, the addition of antidepressants to an ongoing treatment with mood stabilizers will be helpful in only a quarter of patients with bipolar depression. It is also known that the rates of completed suicide in patients with BD are 7.8% in men and 4.9% in women, which could be partially explained by treatment refractoriness. Therefore, despite the pharmacological and psychological strategies to treat patients with mood disorders, how to treat the large number of patients who are refractory to them is still a major challenge. Lack of such knowledge is an important question since treatment-resistant mood disorder patients are associated with greater morbidity, suicide attempts, as well as with extensive use of mood-related and general medical services. Thus, a book on the subject of treatment resistance is key and of great clinical and public health value.