Depression is one of the prevalent and persistent psychiatric illnesses. It brings heavy socioeconomic burden such as healthcare expenditures and even higher suicide rates. Despite many hypotheses about its mechanism have been put forward, so far it is still unclear, not to mention the precise and effective diagnostic or therapeutic methods. In this paper, the current conditions of pathological and pharmacological mechanism of depression were reviewed systematically. Firstly, the most recent hypotheses and metabolomics based research including hereditary, neurotransmitter systems, brain derived neurotrophic factor (BDNF), hyperactivity of the hypothalamic pituitary adrenal (HPA) axis and inflammatory as well as metabolomics were summarized. Secondly, the present situation and development on antidepressant drugs at home and abroad were reviewed. Finally, a conclusion and prospect on the pathological and pharmacological mechanism of depression were provided primarily.