Major depressive disorder (MDD), also known simply as depression, is a mental disorder characterized by at least two weeks of pervasive low mood.
Current estimates are that severe depression affects around 2% of the global population at any given time, currently more than 150 million. The majority of cases don't appear to have an obvious personal and/or societal cause.
The pathophysiology of depression is not yet understood, but the current theories center around monoaminergic systems, the circadian rhythm, immunological dysfunction, HPA axis dysfunction and structural or functional abnormalities of emotional circuits. Source: Wikipedia
Further reading on the biology of depression at Wikipedia
Note: Many of the drugs currently used to treat depression have as-yet-unexplained mechanisms of action. e.g., , , etc etc.