Purpose of Review To review the role of ocular surface epithelial (corneal and conjunctival) ion transporters in the pathogenesis and treatment of dry eye disease (DED). Recent Findings Currently, anti-inflammatory agents are the mainstay of DED treatment, though there are several agents in development that target ion transport proteins on the ocular surface, acting by pro-secretory or anti-absorptive mechanisms to increase the tear fluid film volume. Activation or inhibition of selected ion transporters can alter tear fluid osmolality, driving water transport onto the ocular surface via osmosis. Several ion transporters have been proposed as potential therapeutic targets for DED, including the cystic fibrosis transmembrane conductance regulator (CFTR), calcium-activated chloride channels (CaCCs), and the epithelial sodium channel (ENaC). Summary Ocular surface epithelial cell ion transporters are promising targets for pro-secretory and anti-absorptive therapies of DED.