Drug-resistant depression is usually defined as a depression with unsatisfactory treatment response to two or more adequate antidepressant trials. In further management, antidepressant drug can be switched into one with a broader mechanism of action, combination of two antidepressant drugs can be used or other drug added for an augmentation of antidepressants. Mood stabilizing drugs are frequently employed for augmentation what may show that in the pathomechanism of drug-resistant depression, an unrecognized bipolar depression may play a role. The most frequent physical procedure in drug-resistant depression is electroconvulsive therapy, and new methods include transcranial magnetic stimulation, vagal nerve stimulation and deep brain stimulation.