The elevated concentration of arsenic (As) in the groundwaters of many countries worldwide has received much attention during recent decades. This article presents an overview of the natural geochemical processes that mobilize As from aquifer sediments into groundwater and provides a concise description of the distribution of As in different global groundwater systems, with an emphasis on the highly vulnerable regions of Southeast Asia, the USA, Latin America, and Europe. Natural biogeochemical processes and anthropogenic activities may lead to the contamination of groundwaters by increased As concentrations. The primary source of As in groundwater is predominantly natural (geogenic) and mobilized through complex biogeochemical interactions within various aquifer solids and water. Sulfide minerals such as arsenopyrite and As-substituted pyrite, as well as other sulfide minerals, are susceptible to oxidation in the near-surface environment and quantitatively release significant quantities of As in the sediments. The geochemistry of As generally is a function of its multiple oxidation states, speciation, and redox transformation. The reductive dissolution of As-bearing Fe(III) oxides and sulfide oxidation are the most common and significant geochemical triggers that release As from aquifer sediments into groundwaters. The mobilization of As in groundwater is controlled by adsorption onto metal oxyhydroxides and clay minerals. According to recent estimates, more than 130 million people worldwide potentially are exposed to As in drinking water at levels above the World Health Organization's (WHO's) guideline value of 10 μg/L. Hence, community education to strengthen public awareness, the involvement and capacity building of local stakeholders in targeting As-safe aquifers, and direct action and implementation of best practices in identifying safe groundwater sources for the installation of safe drinking water wells through action and enforcement by local governments and international water sector professionals are urgent necessities for sustainable As mitigation on a global scale.