Optical coherence tomography (OCT) is a noninvasive tool used for measuring tissue at micrometer resolution. It has been extensively applied to ocular pathologies and is now being studied as a biomarker in various neurologic conditions. The retina represents a unique environment for study, with unmyelinated axons that directly synapse into the central nervous system. When trying to quantify axonal degradation in neurologic disease, the currently used imaging modalities are limited in sensitivity and specificity. Early data suggest that several neurologic conditions have pathologic changes in the retinal nerve fiber layer of the eye, creating a potential surrogate marker for neurodegeneration. OCT has the potential to become a noninvasive, reproducible test for axonal degeneration that could become an invaluable tool for measuring the efficacy of potential neuroprotective agents. If the natural history of neurodegeneration, as measured by OCT, can be documented in diseases such as Alzheimer's, Parkinson's and multiple sclerosis, then OCT can be used to measure alterations in the rate of degeneration when treatment is applied. Thus, OCT represents a new, promising technology for documenting outcomes in neuroprotection trials.