The inactivation of coliphage MS2 by iron- and copper-catalyzed Fenton systems was studied to assess the importance of this process for virus inactivation in natural systems and during water treatment by advanced oxidation processes. The influence of H2O2 (3−50 μM) and metal (1−10 μM) concentrations, HO• production, and sunlight on inactivation was investigated. Inactivation was first order with respect to H2O2, but the dependence on the metal concentration was more complex. In the Cu/H2O2 system, the inactivation rate constant kobs increased with added Cu up to 2.5 μM, and then leveled off. This was consistent with Cu saturation of the solution, indicating that only soluble Cu contributed to inactivation. In contrast, inactivation in the Fe/H2O2 system was governed by colloidal iron. Irradiation by sunlight only affected the Fe/H2O2 system, leading to a 5.5-fold increase in kobs (up to 3.1 min−1). HO• production, measured by electron spin resonance, could not account for the observed inactivation in the Fe/H2O2 system. Other oxidants, such as ferryl species, must therefore play a role. Experiments using bulk oxidant scavengers revealed that inactivation occurred by a caged mechanism involving oxidant production by metals located in close proximity to the virus. Overall, our results show that the Fenton/photo-Fenton process may serve as an efficient technology for virus disinfection.