As corneal transplantation has evolved, the spectrum of post-surgical infection has changed and often presents a diagnostic and therapeutic challenge. Lamellar techniques hold the potential of improved outcomes and decreased post-operative complications, however, they create a lamellar interface, which is a potential space for sequestration of infectious organisms. In addition, while keratoprosthesis offers vision to patients who are poor candidates for traditional keratoplasty, infectious complications can be severe and sight threatening. Although antimicrobials remain the mainstay of treatment, definitive management often requires surgical intervention.