The etiology of psychiatric disorders such as depression and schizophrenia remains unclear while, in many aspects, the neuropathology of these disorders has recently been reported to be closely associated with neuroinflammation. Microglia, which are the major players of innate immunity in the CNS, respond rapidly to even minor pathological changes in the brain and may contribute directly to the neuroinflammation by producing various proinflammatory cytokines and free radicals. We and other researchers have recently shown the inhibitory effects of some antidepressants as well as some antipsychotics on the release of inflammatory cytokines and free radicals from activated microglia, both of which have recently been known to cause the synaptic pathology, a decrease in neurogenesis, and white matter abnormalities found in the brains of patients with psychiatric disorders. Microglial activation may not be the primary cause of psychiatric disorders but it may be closely related to the pathology of acute stage of psychiatric disorders. The neuroinflammaiton hypothesis of psychiatric disorders may shed new light on the therapeutic strategy for these disorders.