In this chapter, we summarize up-to-date scientific evidence on the role of apolipoprotein E (apoE = protein; APOE = gene), a 34-kDa protein involved in lipid metabolism, in the pathophysiology process during nerve injury, myelin repair, and nerve regeneration in the peripheral nervous system (PNS) in both in vitro and animal models. We discuss the current epidemiology of neuropathies and experimental models of nerve injury to address the role of neuroprotective compounds in improving nerve regeneration. We also highlight the distinct effects of apoE isoforms in the blood-nerve barrier and myelin remodeling, as well as the potential therapeutic benefits of apoE mimetic peptides. There is a significant knowledge gap regarding how apoE interacts with the transcriptional factor network following nerve injury in the PNS. More studies are needed to address the potential benefits of apoE mimetic peptides to tackle neuropathy and improve clinical outcomes.