Paclitaxel is an antineoplastic drug which acts by enhancing tubulin polymerization. The induction of peripheral neuropathy is the main dose-limiting side-effect of paclitaxel treatment. In this study, the neurotoxic effect of this drug in dorsal root ganglion (DRG) explants was analyzed by measuring the neurite length of DRG explants exposed to nerve growth factor (NGF). The neurotoxic effect of paclitaxel is dose- and time-dependent. Moreover, in DRG dissociated post-mitotic neurons, the molecular and morphological features of paclitaxel-induced cellular death were studied and the DRG neurons were observed to die by necrosis. On the contrary, the proliferating human neuroblastoma SH-SY5Y cells exposed to paclitaxel die by apoptosis, as reported for cortical neurons. The different response to the same stimulus of different neuronal populations underlines the importance of the biochemical and molecular phenotype of the neuronal population in determining cellular behavior and vulnerability to the same noxious stimulus.