Arsenic is a notorious poison classified as a carcinogen, a teratogen and a clastogen that ranks number one on the Environmental Protection Agency's priority list of drinking water contaminants. It is ubiquitous and relatively abundant in the Earth's crust. Its mobilization in waters by weathering, volcanic, anthropogenic or biological activities represents a major hazard to public health, exemplified in India and Bangladesh where 50 million people are acutely at risk. Since basically the origin of life, microorganisms have been exposed to this toxic compound and have evolved a variety of resistance mechanisms, such as extracellular precipitation, chelation, intracellular sequestration, active extrusion from the cell or biochemical transformation (redox or methylation). Arsenic efflux systems are widespread and are found in nearly all organisms. Some microorganisms are also able to utilize this metalloid as a metabolic energy source through either arsenite oxidation or arsenate reduction. The energy metabolism involving redox reactions of arsenic has been suggested to have evolved during early life on Earth. This review highlights the different systems evolved by prokaryotes to cope with arsenic and how they participate in its biogeochemical cycle.