The purpose of this study was to review the current literature on in vivo confocal microscopy of the cornea and to discuss the current clinical indications for its use in microbial keratitis. Review of select recent literature on in vivo confocal microscopy and atypical microbial keratitis. Delayed diagnosis of Acanthamoeba and fungal keratitis is typical, resulting in significant vision loss. This is partially due to the low sensitivity and time delay of corneal cultures. In the hands of an experienced viewer, the confocal microscope has been found to have a sensitivity of up to 90% in the diagnosis of Acanthamoeba keratitis and close to 80% for fungal keratitis. In vivo confocal microscopy is emerging as a tool for rapid diagnoses in severe infectious keratitis with high sensitivity. In addition, it can be used to monitor treatment response, allowing guidance to clinicians for medical or surgical management.