Organophosphorus (OP) compounds are potent acetylcholinesterase (AChE) inhibitors that have found use as both chemical warfare agents (CWAs) and as pesticides. Following inhibition of AChE by OP compounds, a competitive dealkylation reaction of the phosphylated serine residue occurs – a process referred to as aging. Current therapeutic reactivators of OP-inhibited AChE, mainly oximes, are not effective once aging has occurred. For the first time, we have demonstrated in vitro conversion of the aged AChE to the native form using small drug-like molecular therapeutics.  As part of this effort, a diverse library of small molecule therapeutics have been developed to both recover the activity of aged-AChE, termed resurrection, as well as the activity of inhibited-AChE, referred to as reactivation. The structure of such therapeutics is derived from pyridyl-based quinone methide precursors (QMPs), sharing structural similarities to known therapeutic oximes. A structure-activity relationship study of synthesized QMP therapeutics was conducted to determine the effect electron-donating and electron-withdrawing groups have on the efficiency of both processes and to design optimized small molecule therapeutics for in vivo biological efficacy. Our successes will be presented.