Depression is a serious and incapacitating medical illness. MDD is a common condition that is widely frequent in population: community-based surveys conducted in several countries using ICD-10 criteria showed a lifetime prevalence ranging from 6-12%, with an annual prevalence of 3-11%. Current data show that MDD is an incapacitating condition: it is predicted that MDD will be the second cause of incapacitating disease in 2020. In addition, depression is a chronic, recurrent disorder, as nearly 80% of patients relapse after the treatment of an episode. Finally, about one third of patients have treatment-resistant depression (TRD), which is defined as the failure to achieve adequate response of symptoms after two or more antidepressant treatment trials. Various hypotheses propose that MDD is a disorder associated with dysfunction in critical areas related to mood regulation. In fact, two major pathways can be determined here: the cognitive-executive pathway, in which a hypoactive dorso-lateral prefrontal cortex fails to regulate areas related to executive functioning; and the affective-somatic pathway, in which a hyperactive Prefrontal cortex modulates erratically areas related to negative affect and self-awareness. The rationale in using different neurostimulator therapies is based on their mechanisms of inhibiting or enhancing activity in these pathways depending on the area stimulated. The other aspects are biochemical disturbances in certain brain chemicals called neurotransmitters that are thought to be the underlying cause of depressive disorders in general. Major depression is a major psychiatric disorder in which, the prominent symptom is a disturbance of mood which is a constant feeling that is experienced internally and that influences a person’s attitudes, thinking, behavior and perception.