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Cytomegalovirus (CMV) keratitis, albeit an uncommon manifestation of this ubiquitous pathogen, can lead to devastating ocular morbidity. Timely diagnosis and appropriate treatment are also unfortunately uncommon. The purpose of this review is to discuss recently published literature regarding the epidemiology, pathophysiology, diagnosis, and therapy of CMV keratitis.Classic clinical presentations of CMV keratitis are known; however, current investigations further elucidate characteristics of typical versus atypical disease. Ongoing research stems beyond utilizing PCR analysis towards targeted diagnostic studies with advanced imaging modalities as well as modern genotyping techniques. Strong clinical acumen combined with appropriate handling of these modern technologies are proving invaluable for rapid diagnosis and treatment of this virulent pathogen.The current recommended treatment for CMV keratitis is systemic ganciclovir. Astute clinicians must consider this diagnosis in any patient with keratitis, anterior uveitis, and intraocular hypertension. Novel diagnostic techniques should be combined with clinical exam findings to accurately and efficiently diagnose, treat, and monitor progression.