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Internalizing disorders characterized by aberrant self-referential processing and emotion dysregulation.Mindfulness training modulates self-referential processing and reduces internalizing symptoms.Change in self-referential processing may be key mechanism underlying therapeutic effects of mindfulness training.The aim of the current review is to advance the hypothesis that change in self-referential processing is a key but under-examined mechanism through which mindfulness training confers its therapeutic benefits for individuals with internalizing disorders. Consequently, we integrated neuroscientific studies on aberrant self-referential processing in internalizing disorders with contemplative science scholarship examining the effects of mindfulness training on the self-referential system. Reviewing these literatures yielded four major conclusions: (1) internalizing disorders can be characterized by excessive self-referential processing and emotion dysregulation; (2) mindfulness training has moderate effects on reducing internalizing symptoms; (3) mindfulness training promotes the shifting from narrative self-focus to present-centered experiential awareness; (4) such mindfulness-induced changes in self-reference is accompanied by reduced activation in overactive self-referential brain regions that have been implicated in internalizing disorders. Clinical and research implications related to delineating the role of self-referential processing in producing the therapeutic effects of mindfulness training are discussed.