To examine the diagnostic indications and relative merits of a fluid-ventilated, gas-permeable scleral lens for improving vision impaired by irregular astigmatism and for providing a therapeutic environment for managing severe ocular surface disease. After a review of scleral lens development and a description of current design and manufacturing innovations, indications for fitting the Boston Scleral Lens were evaluated based on a retrospective review of all available records of patients fitted with this device, and outcome experiences were described. A total of 875 eyes of 538 patients were fitted with the fluid-ventilated, gas-permeable scleral lens during the past 18 years. Most patients were fitted in the past 4 years. Indications included managing severe ocular surface disease and rehabilitating vision impaired by irregular astigmatism associated with corneal disorders. Rigid gas-permeable contact lenses either were not tolerated or were contraindicated in all eyes. Outcomes included improved vision and reduced ocular pain and photophobia associated with severe ocular surface disease. Scleral lenses promoted healing of persistent epithelial defect (PED) refractory to other treatments and prevented PED recurrence in stem cell-deficient and neurotrophic corneas. Microbial keratitis occurred in 4 of 22 eyes treated with extended scleral lens wear for PED after penetrating keratoplasty. The fluid-ventilated, gas-permeable scleral lens is an important front-line tool for managing many corneal disorders refractory to other treatment measures or otherwise requiring keratoplasty.