Corneal allotransplantation has been the principal surgical treatment for vision loss caused by diseases of the cornea that result in scarring and opacification. Most authors define a “high-risk” cornea as that of a previously failed corneal graft or a cornea with vascularization in at least 2 quadrants. These high-risk corneal transplants have rejection rates approaching 70%, even with maximal local and systemic immune suppression. The management of high risk corneal transplants, which until recently was a slowly evolving field in ophthalmology, remains a highly controversial yet important topic. Management of these high-risk transplants has developed rapidly in the past 10 years. In this review, some of the challenges and controversies associated with high-risk corneal allotransplantation therapy will be discussed.