In addition to clinical studies and cell line models, several rodent models have been developed to elucidate the mechanisms of CIPN and identify potential therapies, including those that measure pathological, electrophysiological, and behavioral outcomes that mimic CIPN in patients. In particular, studies in cultured rat dorsal root ganglion neurons have provided insight into underlying mechanisms of CIPN. However, clinical trials that relied on preclinical animal data have not resulted in consistent benefits of candidate CIPN treatments. Although pain reduction was observed in a recent trial of duloxetine in patients with CIPN, there are BAY 43-9006 currently no FDA approved treatments for CIPN. Due to the rapid advances in stem cell technology, the ability to differentiate human neurons from iPSCs provides an opportunity to create panels of genetically diverse human neurons. Large quantities of neurons from one iPSC line are commercially available for preliminary assay development, drug screens, siRNA screens or functional studies of candidate genes. Upon treatment of iCell Neurons with increasing concentrations of representative neurotoxic agents, we identified reproducible decreases in neurite outgrowth phenotypes. As a proof of concept, we show that decreased PCI-32765 expression of the paclitaxel target TUBB2A by siRNA transfection causes decreased neurite outgrowth after paclitaxel treatment, as expected based on a previous patient study. We show that the variance in neurite outgrowth phenotypes is greater between individuals than the experimental variance within individuals, demonstrating that larger genetic association studies are possible with iPSC-derived neurons. We have applied a human neuronal cell model to the study of chemotherapeutic neurotoxicity. We demonstrate reproducible differences in morphological changes including neurite outgrowth phenotypes, cellular viability and apoptosis among four distinct chemotherapeutic drugs. Importantly, we identified differences among genetically distinct iPSC-derived neurons in the degree of apoptosis for vincristine and cisplatin, relative number of processes for vincristine and relative total outgrowth, process length, and number of branches for paclitaxel. The iPSC-derived neurons are a highly relevant human model currently available for neurotoxicity and much improved from the LCL model used previously for screening and validation. In the human neuronal model, vincristine was the most neurotoxic as measured by morphological changes following treatment.