The adverse impact of groundwater contaminated with arsenic (As) on humans has been reported worldwide, particularly in Asian countries. In this study, we present an overview of the As crisis in the Southeast Asian region where groundwater is contaminated with naturally occurring As and where contamination has become more widespread in recent years. In this region more than 100 million people are estimated to be at risk from groundwater As contamination, and some 700,000 people are known so far to have been affected by As-related diseases. Despite investments exceeding many millions of dollars, there are still substantial knowledge gaps about the prevalence and impact of As, notably in its epidemiology, temporal variations, social factors, patient identification, treatment, etc. Arsenic-affected people in the affected regions also face serious social problems. Of major concern is the fact that many researchers from different countries have been conducting research in SE Asia region but with a lack of coordination, thus duplicating their work. There is an urgent need to coordinate these various studies to ensure better delivery of research outcomes. Further research is needed to improve field testing and monitoring of drinking water sources, and to develop new treatments for chronic As toxicity and new sources of safe drinking water.