We have prepared conductive core-sheath nanofibers via a combination of electrospinning and aqueous polymerization. Specifically, nanofibers electrospun from poly(ε-caprolactone) (PCL) and poly( L -lactide) (PLA) were employed as templates to generate uniform sheaths of polypyrrole (PPy) via in situ polymerization. These conductive core-sheath nanofibers offer a unique system for studying the synergistic effect of different cues on neurite outgrowth in vitro. We found that explanted dorsal root ganglia (DRG) adhered well to the conductive core-sheath nanofibers and generated neurites across the surface when there was a nerve growth factor in the medium. Furthermore, the neurites could be oriented along one direction and enhanced by 82% in terms of maximum length when uniaxially aligned conductive core-sheath nanofibers are compared with their random counterparts. Electrical stimulation, when applied through the mats of conductive core-sheath nanofibers, was found to further increase the maximum length of neurite for random and aligned samples by 83% and 47%, respectively, relative to the controls without electrical stimulation. Combined together, these results suggest the potential use of the conductive coresheath nanofibers as scaffolds in applications such as neural tissue engineering.