Risk factors for corneal transplantation failure include both immunologic factors, such as graft rejection, corneal neovascularization, and peripheral anterior synechiae, as well as non-immunologic factors, such as ocular surface disorders (OSD) and glaucoma. This review highlights the necessity of having healthy ocular surface epithelia, tears, and eyelids. It presents different types of OSD, their underlying pathology, and their impact on native cornea and corneal grafts. In addition, a range of proposed donor and surgical factors influencing surface integrity following corneal transplant are addressed. Current medical and surgical research, both pre- and post-operative that promise to further improve the outcome of corneal grafts in the context of OSD are discussed.