Depression continues to increase at a global scale, and utmost importance has been placed on measures to combat this disease. In Japan, the Ministry of Health, Labor and Welfare has launched priority measures as part of five projects for five diseases, with mental diseases such as depression being newly added to the four diseases so far. Although genetic developmental factors, psychosocial factors, organic (physical) factors, etc. are important as onset factors of depression, neurobiological factors occurring in the brain have recently been elucidated in quick succession. In addition to the conventional monoamine hypothesis, recent studies have offered a hypothesis related to neurotoxicity in the hippocampus owing to a decrease in BDNF (brain-derived neurotrophic factor), as well as observations on the hypofunction of the DLPFC (dorsal lateral prefrontal cortex) and hyperactivity in both the amygdala and subgenual cingulate cortex (Cg25). Depression needs to be understood as a "brain disease" rather than a "mental disease". In recent years, many new diagnostic methods and therapeutic endeavors have been made based on the pathophysiology of the brain. Among them, near-infrared spectroscopy (NIRS) is a new diagnostic technology originating in Japan that is simple and non-invasive, and is useful for differentiating between depression and bipolar disorder. Our study has also revealed that blood flow shows a significant increase in the left dorsolateral prefrontal area as depression is ameliorated, which is considered to be useful for judging the effect of treatment. Regarding methods of physical therapy outside of drug therapy, repetitive transcranial magnetic stimulation (rTMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), and other types of therapy are performed overseas as stimulation therapy to correct functional changes in the brain. In Japan, rTMS has been covered by insurance since June 2019, and it is a boon that treatment options have increased.