Here, we discuss NMNAT2/SARM1 regulation and its role in chemotherapy-induced peripheral neuropathy focusing on three main aspects, namely: (1) NMNAT2/SARM1 balance and its direct role on NAD+ synthesis at cellular level and axonal translocation; (2) NMNAT2/SARM1 regulation of important downstream players that can be involved in neuronal cell death; (3) SARM1 and its role in the immune cells activation that can play a role in neuroinflammation development. The gene discussed is SARM1; the disease is peripheral neuropathy.