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This review describes neuroprotective effects mediated by pre- and post-conditioning-induced processes that act via the quantitative features of the hormetic dose response. These lead to the development of acquired resilience that can protect neuronal systems from endogenous and exogenous stresses and insult. Particular attention is directed to issues of dose optimization, inter-individual variation, and potential ways to further study and employ hormetic-based preconditioning approaches in medical and public health efforts to treat and prevent neurodegenerative disease.