Central corneal pathologies can lead to an irreversible decrease of best corrected visual acuity if not diagnosed and treated appropriately. This article reviews the differential diagnosis of central corneal opacities in the newborn, of central infectious corneal ulcers, and the therapy of sterile, central keratolysis.Authors' personal experience and review of the literature.Flow charts for diagnosis and treatment strategy have been elaborated.Corneal opacities in newborns create an emergency situation. In order to treat successfully and avoid or diminish amblyopia, it is imperative to rule out congenital glaucoma. The aetiology of central corneal ulcers should always be confirmed by positive cultures to be able to treat specifically. When the standard topic therapy fails, one has to consider rare bacteria, parasites, virus, or patients' compliance. The treatment of central sterile keratolysis in rheumatoid arthritis must be intensive and immunosuppression has to be performed early enough in the course of prevent the formation of a descemetocoele or spontaneous corneal perforation.