Aminoglycosides are toxic to both the inner ear hair cells and the ganglion cells that give rise to the eighth cranial nerve. According to recent studies, these cells have a repertoire of molecular responses to aminoglycoside exposure that engages multiple neuroprotective mechanisms. The responses appear to involve regulation of ionic homeostasis, mitochondrial coupling between respiration and ATP generation, and growth factor up-regulation. They also appear to be directed not only at limiting damage but also at maintaining and restoring nerve function. It is suggested in this article that therapeutic strategies emulate these endogenous responses by simultaneously employing: (1) antioxidant (so-called "nutriceutical") therapy; (2) growth factor-based therapy; (3) NMDA receptor antagonism; and (4) modulation of mitochondrial uncoupling protein expression and activation.