The emergence of optical coherence tomography (OCT) technologies has allowed measurements of retinal nerve fiber layer (RNFL) and macular thickness that complement the history and clinical examination in distinguishing forms of acute optic neuropathy and retinal disease. High-resolution Fourier domain OCT has allowed for rapid imaging of the retina as well as three-dimensional imaging and improved volumetric measurements. Ongoing studies of OCT in clinical trials and research examine patterns of axonal degeneration and visual loss over time, and establish the role for OCT and other ocular imaging modalities as structural markers. With the emergence of a variety of OCT techniques, including Fourier Domain OCT, future studies will also help establish the protocols for data analysis to provide meaningful information about changes in structure from baseline. OCT is likely to play an increasing role in multiple sclerosis (MS) trials for measuring both axonal integrity and neuronal preservation.