Schizophrenia is a serious and relatively common mental illness. Its causes are not known in detail, but both genetic and environmental factors are assumed to contribute to the risk of schizophrenia. A number of studies find that the prevalence and incidence are higher in individuals born or raised in city areas than in individuals from rural areas. The causes of this difference are unknown. This paper reviews possible methodological problems as an explanation of these differences and discusses possible candidate risk factors that could underlie urban-rural differences. It is concluded that the causes of urban-rural differences in the risk of schizophrenia are unknown, but that cumulative or repeated exposure during upbringing to factors more common in cities, for instance exposure to pollutants like lead, are hypothetically possible explanations of the urban-rural difference.