Contamination of terrestrial and aquatic ecosystems by arsenic (As) is a very sensitive environmental issue due to its adverse impact on human health. Although not anthropogenic in origin, the problem of As contamination in groundwaters of West Bengal (India) and Bangladesh has been considered of calamitous proportion because significant segment of the population is at high risk, with untold numbers already suffering from irreversible effects of As poisoning. Elsewhere, indiscriminate disposal of industrial and mining wastes has led to extensive contamination of lands, thereby exacerbating the potential for food chain contamination. With greater public awareness of As poisoning in animal and human nutrition, there has been a growing interest in developing regulatory guidelines and remediation technologies for mitigating As-contaminated ecosystems. Although the immediate needs revolve around the stripping of As from domestic water supplies as exemplified by the affected areas in Bangladesh and West Bengal, a remediation scheme should also be explored to be able to cope with pivotal needs to abate the contamination of soils, sediments, and water and the potential to compromise the quality of the food chain. A range of technologies, including bioremediation, has been applied with varying levels of success either to remove As from the contaminated medium or to reduce its biotoxicity. This review provides general overview of the various biogeochemical processes that regulate As bioavailability to organisms, including microbes, plants, animals and humans. In turn, the role of the source term, chemical form, and chemical species of As are discussed as an overture to As bioavailability. Having laid the fundamental mechanisms and factors regulating As bioavailability, we then assembled the various physical, chemical, and biological mitigative methods that have been demonstrated, some being practical, highlighting their special strengths and potential for more effective and economical widespread applications. Because of the complexity involved in dealing with contaminated sites, exacerbated by site characteristics, nature of hydrogeology, source term, chemical form, land use, and so on, no one remedial technology might suffice. Therefore, we have attempted to offer an “integrated” approach of employing a combination of technologies at multiscalar levels, depending on extenuating circumstance, with the aim of securing viable methods, economically and technologically. Future research needs, especially in the area of As bioavailability and remediation strategies, are identified.