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Improvements in all-optical means of monitoring and manipulating neural activity have generated new ways of studying psychiatric disease. The combination of calcium imaging techniques with optogenetics to concurrently record and manipulate neural activity has been used to create new disease models that link distinct circuit abnormalities to specific disease dimensions. These approaches represent a new path towards the development of more effective treatments, as they allow researchers to identify circuit manipulations that normalize pathological network activity. In this review we highlight the utility of all-optical approaches to generate new psychiatric disease models where the specific circuit abnormalities associated with disease symptomology can be assessed in vivo and in response to manipulations designed to normalize disease states. We then outline the principles underlying all-optical interrogations of neural circuits and discuss practical considerations for experimental design.