The effectiveness and selectivity of Fenton degradation of hydrophobic organic compounds (HOCs) can be improved by simultaneous complexation of Fe(2+) and the organic compound with a cyclodextrin or derivatized cyclodextrin. Such selective complexation of a target substrate and a catalytic metal is a crude mimic of enzyme systems. Both beta-cyclodextrin and carboxymethyl-beta-cyclodextrin (CMCD) were able to simultaneously complex Fe(2+) and an aromatic hydrocarbon, such as phenol, polycyclic aromatic hydrocarbons, and polychlorinated biphenyls (PCBs). Degradation of compounds included in cyclodextrins was unaffected by hydroxyl radical scavengers, indicating that the radical was formed at the ternary complex (HOC-cyclodextrin-iron) and in close proximity to the included molecule. Without cyclodextrins, humic acid (HA) decreased degradation efficiency. However, in the presence of CMCD, HA did not inhibit degradation of the target compound. CMCD is capable of removing HOCs from HA binding sites while at the same time complexing Fe(2+). PCBs sorbed to glass were resistant to Fenton degradation, but were significantly degraded using a cyclodextrin modified Fenton system. In all of these systems, the ternary HOC-cyclodextrin-iron complexes effectively direct hydroxyl radical reaction toward the HOC, increasing the efficiency of Fenton degradation. One potential application of such targeted degradation systems is the in situ remediation of hydrophobic organic pollutants in contaminated soil and groundwater or in industrial waste streams.