Abstract: Neural damage or degeneration is at the crux of many diseases, and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration. Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate, and the combination of these factors results in the great regenerative capacity of the peripheral nervous system (PNS) and the poor regenerative capacity of the central nervous system (CNS) following injury. At the core of a neuron’s function is its ability to relay electrochemical signals, and a neuron’s excitability is a key factor in its ability to regenerate. Recent works have focused on the changes in neuronal electrophysiological properties, firing patterns, and ion flux after injury, which differentially activate signaling pathways at the core of regeneration. The role of glia in neuron regeneration has long been studied, but new and expanded signaling pathways are still being discovered. Recent work has demonstrated the ability of glia to modulate neuron firing (Lezmy et al., 2021), which has overlapping implications in a regenerative context. The neuron–glia interactions, and their effects on excitability and pathway activation, are highly context-dependent, but mark an essential frontier in our understanding of neural regeneration and related therapeutics (Figure 1). Here, we will discuss our recent publication and other exciting works in the field.