Atypical antipsychotic agents such as clozapine and risperidone have recently been shown to have immunomodulating properties and effectively reduce inflammation in the central nervous system. Additionally, our laboratory has found these to be effective in reducing disease severity in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. We found that both clozapine and risperidone effectively alter the activation of macrophages and microglia in vitro and in vivo and the functional impact of these alterations include altering the biasing of T cells into Th1, Th2 and Th17 but not Treg subsets. Atypical antipsychotic agents antagonize multiple G protein coupled receptors including dopamine and serotonin receptors, but the precise mechanism by which they alter macrophage and microglial activation is unclear. This research focuses on the specific downstream signalling pathways including those mediated by cAMP, phospholipase C, and AKT to determine the precise mechanism by which treatment with atypical antipsychotic agents are able to suppress neuroinflammation and significantly reduce disease in experimental autoimmune encephalomyelitis.