OBJECTIVE The purpose of this study was to evaluate the immunology, pathogenesis and therapy of Acanthamoeba keratitis. METHODS The recent development of an animal model of Acanthamoeba keratitis and its impact on the medical treatment and immunology of Acanthamoeba keratitis was reviewed. RESULTS After initial reports, Acanthamoeba infection of the cornea remained a rare disease until an association with contact lens wear was first recognized. Although the disease is closely associated with contact lens wear, it appeared that the contaminated solutions that were coming into contact with the lenses caused the disease. All types of contact lenses can be associated with development of Acanthamoeba keratitis. Therefore, the contact lens serves as a carrier of Acanthamoeba to the surface of the eye. The typical patient with Acanthamoeba keratitis is a young healthy individual who is either a contact lens wearer or has had significant exposure to water contaminated with Acanthamoeba. There are several risk factors such as corneal trauma, contaminated solution and contact lenses that have been reported to be associated with Acanthamoeba keratitis. In spite of significant improvement in the diagnosis of Acanthamoeba keratitis, progress in developing and utilizing effective antimicrobial agents for treating this disease have been disappointing. A growing body of evidence suggests that the mammalian immune system, if properly activated, is capable of preventing and controlling ocular infections. CONCLUSIONS In order to develop effective immunotherapeutic modalities, and to better understand the immune effector mechanisms that protect the cornea against Acanthamoeba infection, it is necessary to fully characterize and evaluate the immunobiology of Acanthamoeba keratitis.