Results obtained from direct numerical simulations are presented to examine effects due to differential diffusion on reacting scalars in isotropic, decaying turbulence. In the simulations fuel and oxidant react via a one-step, isothermal reaction (activation energy is set to zero). The results demonstrate that effects due to differential diffusion decrease with increasing Reynolds numbers and increase with increasing Damkohler number values. A principal issue investigated in this paper is whether a conditional moment closure-flamelet approach can be applied to accurately account for differential diffusion effects. The results show that the neglect of the conditional fluctuations in the modeling amplifies the influence of differential diffusion and leads to incorrect dependence on the Reynolds number. The paper investigates the different terms representing the conditional fluctuations in the model equations. Also investigated is the influence of differential diffusion on the validity of the boundary conditions set in conserved scalar space.