We are presently witnessing the largest mass poisoning in history due to arsenic in groundwater used for drinking in Southeast Asia. The arsenic is native to rocks of the Himalaya Mountains and is transported down the major river systems of the region in the sediment load and deposited within the large sedimentary basins that dominate the low-lying landscapes of the region. Post-deposition, arsenic is released from the solid-phase and enters pore-water within the soils and is subsequently transported downward into the underlying aquifer. The release and transport processes, however, are heterogeneously distributed in time and space, and ultimately are controlled by a coupling of hydrologic and biogeochemical processes that transpire to give the high arsenic concentrations in groundwaters. We have used a multifaceted approach, that includes field measurement of physical and biogeochemical processes and characteristics, experimentation, and modeling, to deduce the governing processes controlling the migration of arsenic and leading to the largest mass poisoning in history.