Acanthamoeba is a free-living, fresh-water protozoan that can cause severe corneal disease. Acanthamoeba keratitis can closely mimic epithelial and stromal Herpes simplex keratitis. Three cases of severe keratitis, were referred for treatment. One patient presented with a pseudodendritic epithelial lesion that gradually progressed to stromal involvement. A second patient presented with central stromal infiltrate and necrosis, while a third exhibited features of a disciform lesion with the later development of an immune ring. Acanthamoeba was recovered from the cornea in each case. The distinctive characteristics of the history and clinical findings in Acanthamoeba keratitis can aid the clinician in distinguishing between these two clinical entities. Cytopathology and special staining and culture techniques can confirm the diagnosis.