Abstract Objective To review the available evidence for the use of confocal microscopy in diagnosing infectious keratitis and for other applications for ophthalmic practice. Methods A MEDLINE search of the peer-reviewed literature for the years 1990 to 2001 yielded 94 citations. The search was limited to studies of human subjects published in English with abstracts. The Ophthalmic Technology Assessment Committee Cornea Panel evaluated these 94 articles for possible clinical relevance and selected 51 (54%) for content review by the panel members. Of these 51 articles, 24 were selected for the panel methodologist to review and rate according to the strength of evidence. Results Of the 24 articles, 21 (87.5%) were classified as case reports or case series and were rated as level III evidence. Three articles were classified as independent, masked, or objective comparisons performed in a narrow spectrum of patients or in a nonconsecutive series of patients and were rated as level II evidence. No studies were rated as level I evidence, defined as an independent masked comparison of an appropriate spectrum of consecutive patients. Conclusion Confocal microscopy is a new technology with clinical applications in ophthalmology. Although confocal microscopy has been used in other fields of medicine, the optical transparency of the cornea and other structures of the eye provides a unique opportunity to apply this technology. The targeted literature review of 24 articles found no level I studies to support the use of confocal microscopy in the management of eye disorders. Three level II studies pertained to promising clinical applications of the confocal microscope and provided evidence that supports the use of confocal microscopy as an adjunctive modality for diagnosing Acanthamoeba keratitis. The remaining 21 articles, rated as level III evidence, focus on the use of confocal microscopy to facilitate the diagnosis of infectious keratitis, including amoebic and fungal, but currently there are no definitive studies of its role in the differential diagnosis of this condition. There are also level III studies that support the use of the confocal microscope in refractive surgery. Facilitating the diagnosis of infectious keratitis and applying the confocal microscope to refractive surgery may hold the greatest promise of this new technology.