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Complement system is one of the most important defense mechanisms of the innate immune system. In addition to their roles in immune regulation, complement proteins are also involved in neurodevelopment and adult brain plasticity. Complement dysregulation has been shown in neurodevelopmental disorders including schizophrenia and autism spectrum disorder as well as in mood disorders. A number of clinical as well as genetic studies suggest the role of complement proteins in the cortical thinning and excessive synaptic pruning frequently associated with schizophrenia. The changes in complement proteins are also associated with the pathophysiology of autism spectrum disorder, major depressive disorder and bipolar disorder, but warrant further research. In addition, rodent models suggest a strong case for complement system in anxiety-like behavior. In this article, we review the recent findings on the role of complement system in neuropsychiatric disorders. The possible uses for future complement targeted therapies are also discussed.