Neuropsychiatric diseases, such as schizophrenia, depression and autism, are a huge burden on society, impairing the health of those affected, as well as their ability to learn and to work. After half a century of concerted effort, researchers are now making progress towards defining the biological basis of these diseases. Technological advances in the areas of genomics and large-scale studies, as well as the development of new animal models, are improving our understanding of these diseases and are offering the prospect of fundamentally different options for treatment.