Schizophrenia is a psychiatric disorder characterized by distortions of thinking and perception, with no strictly pathognomonic symptoms that can be divided into positive, negative, and cognitive symptom domains. People with schizophrenia have, between others, a reduced life expectancy and cardiorespiratory and muscular fitness and increased risk of cardiovascular disease, metabolic syndrome, obesity, hypertension, and hyperlipidemia compared to the general population. Furthermore, the economic burden of mental disorders including schizophrenia is evident and it is expected to increase to more than double by 2030. Therefore, reducing the growing burden of mental disorders such as schizophrenia should be a health priority. Improved prevention and treatment are two key factors that may reduce the burden of schizophrenia. Pharmacological- and psychotherapy-based interventions have been traditionally considered for treating schizophrenia disorders; however, there is an increasing amount of scientific evidence confirming that physical activity and physical exercise should be highly considered in prevention and treatment of schizophrenia disorders. In this chapter, we aim to summarize and discuss the research progress of physical activity and exercise in prevention and treatment of schizophrenia disorder. Specifically, we summarized and discussed the research progress of the prognostic use of physical activity for incident schizophrenia; the importance of other outcomes typically improved by physical activity/exercise such as obesity and fitness (cardiorespiratory and muscular fitness) for future schizophrenia; the research progress of the evidence of the benefits of exercise in people with schizophrenia disorders differentiating between effects of exercise on varied health outcomes, cognitive functioning, and cardiorespiratory fitness; and finally the clinical practice recommendations.