Moyamoya angiopathy (MMA), a rare and enigmatic disease, has intrigued clinicians and researchers for over six decades since its first description. In this past decade, although significant strides have been made in genetic research in MMA, a low penetrance of the phenotype, has led researchers to invoke a geo-environmental agent in its causation. The geographical prevalence of MMA and geospatial maps, food habits, possible sources of industrial pollutant exposure, and groundwater data were examined. The clustering of cases in east Asia, Bangladesh and certain foci in the United States, corresponded with the high levels of arsenic in food and water sources. We propose a hypothesis of an association between arsenic exposure and MMA. The extrapolated genetic and molecular effects of arsenic that lead to moyamoya angiopathy are proposed in this paper. Arsenic could be the elusive environmental agent catalyzing the pathogenesis of MMA. This hypothesis could stimulate further research into the role of arsenic in the pathogenesis of MMA. Implementation of mitigation strategies could result in a reduction in the incidence of the disease.