Evidence from experiments with adult rodents chronically treated with ethanol via either repetitive binges or continuous intake/exposure supports the occurrence of brain oxidative stress and, at least in binge intoxication/rat models, its essential causative role in neurodamage. However, pharmacological antagonism experiments reveal that N-methyl-D-aspartate (NMDA) receptor-dependent excitotoxicity is not responsible for adult mammalian brain neurodegeneration caused by repetitive binge ethanol intoxication and withdrawals. Since NMDA receptor antagonists apparently are untested with respect to neuronal death/loss in continuous intake/ingestion rodent models, e.g., ethanol/water or ethanol/liquid diets, it is therefore erroneous to assert, as is often done, that excitotoxicity is an important mechanism for ethanol-induced adult mammalian brain (neuronal) damage. Alternatively, results from several laboratories indicate that neurodegeneration due to chronic binge ethanol exposure/withdrawal may be dependent on redox transcription factor signaling and neuroinflammatory/oxidative stress pathways (increased arachidonic acid mobilization and pro-inflammatory cytokines; decreased anti-inflammatory cytokines) downstream of microglial/astroglial activation and moderate yet significant brain edema.