Objective: To review the available evidence for the neuroprotective qualities of brimonidine tartrate in optic nerve and retinal injury. Methods: References for this study were obtained by running a search of the PubMed database using keywords brimonidine, neuroprotection, ischemic optic neuropathy, and α2-adrenergic agonists. References focusing on ocular hypertension were excluded. Results: Forty-eight articles addressing 1 of 4 criteria for neuroprotection were included. The literature confirms that brimonidine therapy meets the first 3 criteria for neuroprotection: receptors on its target tissues, adequate penetration into the vitreous and retina at pharmacologic levels, and induction of intracellular changes that enhance neuronal resistance to insults or interrupt apoptosis in animal models. Brimonidine did not meet the final neuroprotective criterion of success in humans. Conclusions: Experimental evidence has demonstrated that brimonidine is a potential neuroprotective agent. However, to date, clinical trials have failed to translate into similar efficacy in humans.