Treatment-resistant major depression and bipolar disorder are highly prevalent and disabling conditions associated with substantial morbidity and mortality. The assessment and management of refractory patients with mood disorders is a major clinical challenge for mental health providers. Part of the Oxford Psychiatry Library (OPL) series, this pocketbook provides a concise view of the current definitions, assessment and evidence-based management of treatment-resistant mood disorders and reviews novel therapeutic targets for mood disorders, which may enhance the therapeutic armamentarium of clinicians in the near future. The pocketbook serves as a useful guide for mental health practitioners, including psychiatrists, clinical psychologists, trainees, and interested primary care physicians.