The pathophysiology of multiple sclerosis (MS) is characterized by demyelination, which culminates in a reduction in axonal transmission. Axonal and neuronal degeneration seem to be concomitant features of MS and are probably the pathological processes responsible for permanent disability in this disease. The retina is unique within the CNS in that it contains axons and glia but no myelin, and it is, therefore, an ideal structure within which to visualize the processes of neurodegeneration, neuroprotection, and potentially even neurorestoration. In particular, the retina enables us to investigate a specific compartment of the CNS that is targeted by the disease process. Optical coherence tomography (OCT) can provide high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and, we believe, is ideal for precisely modeling the disease process in MS. In this Review, we provide a broad overview of the physics of OCT, the unique properties of this method with respect to imaging retinal architecture, and the applications that are being developed for OCT to understand mechanisms of tissue injury within the brain.