Fluid-ventilated, gas-permeable scleral lenses are a valuable front-line tool in the management of severe ocular surface disease. In addition to enhancing vision, they have the potential to reduce greatly the disabling ocular pain and photophobia associated with SJS, TEN, and ocular cicatricial pemphigoid. They are also useful in healing some PEDs that are refractory to all other treatment strategies and in reducing PED recurrence in stem cell-deficient and neurotrophic corneas. The therapeutic benefits of these lenses are provided by the oxygenated aqueous environment they create over the corneal epithelium. The oxygenated precorneal fluid compartment that is maintained at neutral pressure protects the epithelial surface from the desiccating effects of exposure to air and the friction generated by blinking and avoids the shearing forces generated during the blink-induced movement of soft lenses.