Depression is characterized by functional insufficiency of the right hemisphere combined with its physiological overactivation. This paradox can be solved in the frame of the general concept of brain laterality. According to the present assumption, the left hemisphere organizes any information in an unambiguous monosemantic context, and this process requires an additional activation of the brain cortex in order to restrict natural relationships between objects and events. On the contrary, the right hemisphere organizes any information in the polysemantic context based on the simultaneous capture of the numerous natural relationships between elements of information. In healthy creative subjects this process does not require additional physiological activation of the cortex. In depression the physiological overactivation of the right hemisphere reflects the unsuccessful effort to overcome its functional insufficiency.