Complex, polygenic phenotypes in psychiatry hamper our understanding of the underlying molecular pathways and mechanisms of many diseases. The unknown aetiology, together with symptoms which often show a large variability both across individuals and over time and also tend to respond comparatively slowly to medication, can be a problem for patient treatment and drug development. We argue that neuroimaging has the potential to improve psychiatric treatment in two ways. First, by reducing phenotypic complexity, neuroimaging intermediate phenotypes can help to identify disease-related genes and can shed light into the biological mechanisms of known risk genes. Second, quantitative neuroimaging markers-reflecting the spectrum of impairment on a brain-based level-can be used as a more sensitive, reliable and immediate treatment response biomarker. In the end, enhancing both our understanding of the pathophysiology of psychiatric disorders and the prediction of treatment success could eventually optimise current therapy plans.