Chronic graft-versus-host disease (cGvHD) is a major concomitant phenomenon in recipients of allogeneic hematopoietic stem cell transplantations, affecting multiple organ systems including the eye. Ocular structures, such as lacrimal gland, conjunctiva, and eyelids with meibomian glands, are frequently involved with clinical features ranging from dry eyes and common inflammatory conjunctival disease to severe complications like corneal ulcerations or even perforations. We present 2 patients with complicated courses of ocular cGvHD. In both cases, keratoconjunctivitis sicca refractory to systemic immunosuppressive therapy and to conventional topical treatment resulted in progressive binocular corneal melting and finally repeated perforations. According to our 2 cases and to the current pathophysiological understanding, we discuss possible strategies for the treatment and prevention of ocular cGvHD complications.