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The Default Mode Network (DMN) is one of the large-scale networks of the brain that is anatomically defined well. This network that is active during rest state, is associated with stimulus-independent thought, self-reflection and autobiographical memory retrieval. The regions of DMN include medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), inferior parietal lobule (IPL), lateral temporal cortex (LTC) and hippocampal formation (HF). This network consists of two subsystems: the medial temporal lobe subsystem, which provides data from previous experiences and the medial prefrontal subsystem, which uses this information during the construction of self-relevant and stimulus-independent thoughts. Studies have shown that DMN have neuroplasticity in front of kinds of experiences and its function is impaired in some of the diseases and disorders such as schizophrenia, depression, autism spectrum, and Alzheimer. Also, this network is effective in biological and psychological treatments. In this article, after reviewing the history and anatomy of the DMN, the focus will be on DMN’s functions, its normal changes in development, and its changes in a variety of diseases and disorders. Finally, to the clinical application of these findings will be discussed