High-arsenic groundwater widely spreads in the world, which has posed a great threat to human health. Mechanisms of arsenic mobilization in aquifer systems have been considered to be worldwide scientific issues. We outline characteristics of spatial distribution of high-arsenic groundwater and arsenic enrichment mechanisms. Controls of dissolved organic matter and groundwater flow on arsenic mobilization in groundwater are reviewed and discussed. Recent studies reveal synergistic effect of dissolved organic matter and microbial processes on genesis of high arsenic groundwater. Spatial and temporal variations of higharsenic groundwater and anthropogenic activities affecting the high-arsenic groundwater distribution have recently been characterized, and gradually become the hot topics in this field. These aspects are of great significance in enriching our understanding of transportation and transformation in aquifer systems and finding low-arsenic water resources for sustainable water development in arsenic-affected areas.