Colchicine or vincristine depolymerize microtubules, an action which blocks neuron axonal transport. Thus, these chemicals showed selective neurotoxicity in hippocampal neurons. However, the mechanism of neurotoxicity by these antimicrotubule agents has remained unclear. Our previous studies have suggested that colchicine-induced hippocampal neuron death is caused by incremental increases in intraneuronal free zinc. We have demonstrated that zinc transporter 3 gene deletion ( ZnT3 ^−/−) reduces dentate granule cell death after colchicine injection. This ZnT3 ^−/−-mediated reduction of dentate granule cell death was accompanied by a decrease in the incidence of oxidative injury. Unexpectedly, we found that ZnT3 ^−/− mice contain a higher glutathione (GSH) level in the hippocampal neurons than wild type mice. Thus, ZnT3 ^−/− mice showed less neuronal GSH depletion by colchicine injection, and thus less neuronal death. These results suggest that the higher levels of neuronal GSH in ZnT3 ^−/− mice result in less dentate granule cell death after colchicine injection. In addition to colchicine, our lab also demonstrated that a chemotherapeutic agent, pacritaxel (Taxol), which is a microtubule stabilizing agent, depleted vesicular zinc in the presynaptic terminals and induced a reduction of neurogenesis. Therefore, in the present review, we discussed how antimicrotubule agent-induced neurotoxicity and cognitive impairment is associated with zinc dyshomeostasis in the brain.