<p>Evidence has accumulated that youth, the period between 12–25 years, may constitute a crucial period for the early detection and intervention of mental disorders. Thus, there is emerging evidence that targeted psycho-social and pharmacological interventions have potential to improve clinical outcomes in at-risk individuals as well as in youths with a first-episode of mental illness. However, while support for the early intervention paradigm has gained momentum, an explanatory framework for the emergence of mental disorders as well as for the mechanisms of preventive interventions is currently not available. Here, I will outline a neurobiology of early intervention that will highlight the importance of linking emerging psychopathology with developmental neuroscience and systems biology. Specifically, I will propose that critical periods during late brain development in combination with environmental exposures could account for the elevated occurrence of psychosis, affective disorders, substance abuse and personality disorders. In addition, the neurobiological mechanisms underlying critical periods could be important for understanding the potential of preventive interventions and the identification of biomarkers. Together, a neurobiological grounding of early intervention could provide a conceptual and empirical framework to advance early detection and prevention of mental disorders during youth.</p>