This review is on arsenic in agronomic systems, and covers processes that influence the entry of arsenic into the human food supply. The scope is from sources of arsenic (natural and anthropogenic) in soils, biogeochemical and rhizosphere processes that control arsenic speciation and availability, through to mechanisms of uptake by crop plants and potential mitigation strategies. This review makes a case for taking steps to prevent or limit crop uptake of arsenic, wherever possible, and to work toward a long-term solution to the presence of arsenic in agronomic systems. The past two decades have seen important advances in our understanding of how biogeochemical and physiological processes influence human exposure to soil arsenic, and this must now prompt an informed reconsideration and unification of regulations to protect the quality of agricultural and residential soils.