For the purpose of developing new oxime reactivators of acetylcholinesterases (AChE) that have been inhibited by organophosphorus agents, emphasis was given to the finding that the lipophilic nature of fluorinated compounds is responsible for their enhanced transport across the blood brain barrier (BBB). As a result, we have designed and synthesized the fluorinated oxime derivatives, which quantum mechanical calculations suggest should have a greater lipophilicity and BBB permeability than their non-fluorinated analogs. Among the compounds explored in this study, 4 was found to have the highest potency for reactivation of paraoxon-inhibited housefly (HF) AChE.