The widespread occurrence of high inorganic arsenic in natural waters is attributed to human carcinogen and is identified as a major global public health issue. The scale of the problem in terms of population exposure (36 million) and geographical area coverage (173 × 103 Km2) to high arsenic contaminated groundwater (50–3200 μgL−1) compared to the National drinking water standard (50 μgL−1) and WHO recommended provisional limit (10 μgL−1) is greatest in the Holocene alluvium and deltaic aquifers of the Bengal Delta Plain (Bangladesh and West Bengal, India). This large-scale 'natural' high arsenic groundwater poses a great threat to human health via drinking water. Mobilization, metabolism and mitigation issues of high arsenic groundwater are complex and need holistic approach for sustainable development of the resource. Mobilization depends on the redox geo-chemistry of arsenic that plays a vital role in the release and subsequent transport of arsenic in groundwater. Metabolism narrates the biological response vis-à-vis clinical manifestations of arsenic due to various chemical and biological factors. Mitigation includes alternative source for safe drinking water supply. Drinking water quality regulatory standards as well as guidelines are yet to cover risk assessments for such metal toxicity. Lowering of the ingested inorganic arsenic level and introduction of newer treatment options (implementation of laterite, the natural material) to ensure safe water supply (arsenic free and/or low arsenic within permissible limit) are the urgent need to safe guard the mass arsenic poisoning and internal arsenic related health problems.