Abstract. The historical accumulation and improper disposal of anthropogenic waste materials and by-products have caused widespread contamination of groundwater and soils across the world. To mitigate uranium (U) contamination in groundwater, nanoparticulate iron sulfide minerals have received recent attention as potentially effective agents to retard uranium mobilization. This presentation will discuss the role of iron sulfide as an oxygen scavenger, the thermodynamic and kinetic constraints that control uranium mobility, and the adverse effects caused by iron sulfide oxidation processes. Results from both experimental and molecular modeling investigations of uraninite (UO2) oxidative dissolution will be presented to probe uranium transformation at solid-aqueous interfaces. The results allow us to better understand and predict the fate and transport of uranium during periods of persistent oxygen intrusion in heterogeneous groundwater systems.