There is a pressing need for more effective nonaddictive treatment options for pain. Pain signals are transmitted from the periphery into the spinal cord via dorsal root ganglion (DRG) neurons, whose excitability is driven by voltage-gated sodium (Na) channels. Three Na channels (Na1.7, Na1.8, and Na1.9), preferentially expressed in DRG neurons, play important roles in pain signaling in humans. Blockade of these channels may provide a novel approach to the treatment of pain, but clinical translation of preclinical results has been challenging, in part due to differences between rodent and human DRG neurons. Human DRG neurons and iPSC-derived sensory neurons (iPSC-SNs) provide new preclinical platforms that may facilitate the development of novel pain therapeutics.