The trigeminal nerve gives rise to the corneal subbasal nerve system, which plays a crucial role in sensations of touch, pain, and temperature and in ocular healing processes. Technological advancements in instruments, in particular in vivo confocal microscopy and aethesiometry, have allowed for the structural and functional evaluation of corneal nerves in health and disease. Through application of these technologies in humans and animal models, structural and functional abnormalities have been detected in several ocular and systemic disorders, including dry eye disease (DED), glaucoma, migraine, and fibromyalgia. However, studies across a number of conditions have found that structural abnormalities do not always relate to functional abnormalities. This review will discuss instruments used to evaluate corneal nerves and summarize data on nerve abnormalities in a number of ocular and systemic conditions. Furthermore, it will discuss potential treatments that can alleviate the main manifestations of nerve dysfunction, namely ocular surface pain and persistent epithelial defects.Copyright © 2020. Published by Elsevier Ltd.