There is increasing evidence for the cytokine hypothesis, which states that exposure to elevated cytokines in utero due to maternal immune activation is a major risk factor for the development of schizophrenia later in life. This is supported by numerous epidemicologic studies that connect multiple infections with schizophrenia emergence. Furthermore, cytokines are critically involved in early neurodevelopment and deviations from the norm can result in abnormal neuroanatomy and brain chemistry. Animal models of schizophrenia also support the critical role of developmental neuroinflammation in predisposing the brain to anatomical and behavioral abnormalities. Although there is strong evidence for the critical role of cytokines, they most likely work with other contributing risk factors such as genetic predisposition. New evidence indicates that cytokine exposure in utero may prime the brain and that a second stressor during adolescence, referred to as a second hit, may activate existing developmental vulnerabilities resulting in the emergence of clinical schizophrenia. Further knowledge of these pathogenic processes and risk factors could be very instrumental in reducing risk and slowing emergence of schizophrenia.