Despite the improving results that have been noted with penetrating keratoplasty, graft failure remains a significant problem. The causes of graft failure are quite varied. Primary donor failure, surgical complications, intraocular lens complications, persistent epithelial defects, allograft rejection, infection, glaucoma, trauma, and recurrences of primary corneal dystrophies are common etiologies. In this article, a critical review of the available literature concerned with the factors influencing the many causes of graft failure and their management is provided.