Evidence for low-dose health effects of Arsenic (As) in humans is still controversial and presents a major public health issue in several countries worldwide. It is not clear yet, whether there is a lower safe threshold for arsenic in drinking water among other possible sources such as food, below which, exposures are not harmful. In Uruguay, safe drinking water is supplied to 94% of the population by a state company (OSE) and As levels in workplaces and food are officially regulated. This paper aims to present and discuss the issues regarding arsenic exposure risks to the environment and human population, which are being addressed in a multidisciplinary manner in Uruguay since 2007. An overview is given on both the background and the current situation, presenting reports and research studies conducted on these problems by various academic, state, and private institutions that deal with regulations, surveillance, and health care. Scientific research on geogenic As levels in groundwater indicates As levels above those recommended by the WHO for drinking water (10 μg L-1) in different Uruguayan aquifers. There is a lack of baseline studies concerning Uruguayan residents that are exposed to As in drinking water over time. Furthermore, there is a need for data on environmental chemical exposure that could be associated with disease or death in the country. In addition, only a few As risk exposure assessment studies in children, adults, and workers using biomarkers in urine are available. Furthermore, this paper presents As levels in a rice growing region and the spatial distribution of groundwater arsenic data compared to a national cancer atlas database as ongoing research advances. Multidisciplinary research projects and local future actions are also described. This contribution constitutes a first attempt to develop a feasible health risk assessment of low-dose arsenic exposure in this Latin-American country.