Increasing incidence and awareness of arsenic in many alluvial aquifers of South-east Asia has raised concern over possible arsenic in the Lower Mekong Basin. Here, we have undertaken new research and reviewed many previous small-scale studies to provide a comprehensive overview of the status of arsenic in aquifers of Cambodia and the Cuu Long Delta of Vietnam. In general natural arsenic originates from the Upper Mekong basin, rather than from the local geology, and is widespread in soils at typical concentrations of between 8 and 16 ppm; (dry weight). Industrial and agricultural arsenic is localised and relatively unimportant compared to the natural alluvial arsenic. Aquifers most typically contain groundwaters of no more than 10 μg L−1, although scattered anomalous areas of 10 to 30 μg L−1 are also quite common. The most serious, but possibly ephemeral arsenic anomalies, of up to 600 μg L−1, are associated with iron and organic-rich flood-plain sediments subject to very large flood-related fluctuations in water level, resulting in transient arsenopyrite dissolution under oxidizing conditions. In general, however, high-arsenic groundwaters result from the competing interaction between sorption and dissolution processes, in which arsenic is only released under reducing and slightly alkaline conditions. High arsenic groundwaters are found both in shallow water-tables, and in deeper aquifers of between 100 and 120 m depth. There is no evidence of widespread arsenicosis, but there are serious localised health-hazards, and some risk of low-level arsenic ingestion through indirect pathways, such as through contaminated rice and aquaculture. An almost ubiquitous presence of arsenic in soils, together with the likelihood of greatly increased groundwater extraction in the future, will require continuing caution in water resources development throughout the region.