Depression is considered resistant when two treatment attempts with antidepressants from different classes fail to produce significant clinical improvement. In cases of treatment-resistant depression, it is recommended to reevaluate the diagnosis, clarify comorbidity, substance abuse and lack of compliance. Regarding treatment, evidence is sparse, but switching to a different antidepressant, and combination or augmentation with another agent, admission and treatment with ECT are the options. The choice of treatment must be based on the characteristics of the depression, the severity of treatment resistance and side effects.