It is generally accepted that antidepressants are ineffective in as many as 20 to 30 percent of patients with major depression. In Japan, the term "refractory" is commonly used to refer to a patient who does not respond to adequate treatment for depression, mainly standard pharmacotherapy. Factors associated with refractory depression are multiple. Refractory depression can be divided into several states, such as slightly depressive, neurotic, and residual. A variety of approaches to the refractory patient, that is pharmacotherapy, somatic therapy and psychotherapy is presented.