The resting state of the human brain is intrinsically organized by the so-called default mode network (DMN) which comprises cortical midline structure as well as lateral parietal and temporal areas. The activity of this system increases during self-oriented thinking, e.g. during a resting state but decreases during externally oriented attention and specific cognitive tasks. This review article provides a historical and methodological outline of the DMN model and describes its functional anatomy and putative functions. Based on the empirical literature the clinical implications of alterations of the DMN architecture and its role in various mental disorders are discussed.