Bilateral corneal blindness with severe dry eye disease (DED), total limbal stem cell deficiency with underlying corneal stromal scarring and vascularization, combined with adnexal complications secondary to chronic cicatrizing conjunctivitis is a highly complex situation to treat. In such eyes, procedures such as penetrating keratoplasty alone or combined with limbal stem cell transplantation are doomed to fail. In these eyes, keratoprosthesis (Kpro) or an artificial cornea is the most viable option, eliminating corneal blindness even in eyes with autoimmune disorders such as Stevens–Johnson syndrome, ocular mucous membrane pemphigoid, Sjogren’s syndrome, and nonautoimmune disorders such as chemical/thermal ocular burns, all of which are complex pathologies. Performing a Kpro in these eyes also eliminates the need for systemic immunosuppression and may provide relatively early visual recovery. In such eyes, the donor cornea around the central cylinder of the Kpro needs to be covered with a second layer of protection to avoid desiccation and progressive stromal melt of the underlying cornea, which is a common complication in eyes with severe DED. In this review, we will focus on Kpro designs that have been developed to survive in eyes with the hostile environment of severe DED. Their outcomes in such eyes will be discussed.