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M ental disorders such as schizophrenia, bipolar illness, and depression have become the predominant chronic diseases of young people, accounting for approximately 40% of the medical burden for people aged 15–44 in the United States and Canada. Research is transforming our understanding of these disorders, as exemplified in the articles in this Review Series. Important, “disruptive” insights into pathophysiology are emerging from studies addressing these illnesses as brain disorders, developmental disorders, and complex genetic disorders — rather than only as psychological conflicts or chemical imbalances, as they were considered in the past. Current medications are not sufficient for most patients. A new and deep understanding of the pathophysiology of these disabling disorders is our best hope for a new generation of treatments that will help patients to recover.