Oxygenation of aromatic rings using O-2 is catalyzed by several non-heme carboxylate-bridged diiron enzymes. In order to provide a general mechanistic description for these reactions, computational studies were carried out at the ONIOM(B3LYP/BP86/Amber) level on the non-heme diiron enzyme benzoyl coenzyme A epoxidase, BoxB. The calculations revealed four possible pathways for attacking the aromatic ring: (a) electrophilic (2e(-)) attack by a bis(mu-oxo)-diiron(IV) species (Q pathway); (b) electrophilic (2e(-)) attack via the sigma* orbital of a mu-eta(2):eta(2)-peroxo-diiron(III) intermediate (P sigma* pathway); (c) radical (1e(-)) attack via the pi*-orbital of a superoxo-diiron(II,III) species (P pi* pathway); (d) radical (1e(-)) attack of a partially quenched bis(mu-oxo)-diiron(IV) intermediate (Q' pathway). The results allowed earlier work of de Visser on olefin epoxidation by diiron complexes and QM-cluster studies of Liao and Siegbahn on BoxB to be put into a broader perspective. Parallels with epoxidation using organic peracids were also examined. Specifically for the BoxB enzyme, the Q pathway was found to be the most preferred, but the corresponding bis(mu-oxo)-diiron(IV) species is significantly destabilized and not expected to be directly observable. Epoxidation via the P sigma* pathway represents an energetically somewhat higher lying alternative; possible strategies for experimental discrimination are discussed. The selectivity toward epoxidation is shown to stem from a combination of inherent electronic properties of the thioacyl substituent and enzymatic constraints. Possible implications of the results for toluene monooxygenases are considered as well.