OBJECTIVE The precise mechanisms controlling the depth and extent of fluorescence signal associated with superficial punctate corneal staining remain unclear. Despite this scientific uncertainty, within the past decade there has been a shift in both medical marketing materials and in the peer-reviewed literature to attempt to extrapolate an observation of superficial punctate fluorescence to suggest compromised corneal integrity. This review presents a survey of the peer-reviewed scientific literature around superficial punctate corneal fluorescein staining. RESULTS A comprehensive literature search was conducted for peer-reviewed manuscripts including data around corneal staining, and the results from this search synthesized. A brief historical review of the use of fluorescein dye as a diagnostic tool is provided. A detailed evaluation is made of the evidence supporting or refuting various proposed mechanisms for punctate corneal fluorescein staining, and the implications for corneal health and disease. Finally, future research directions in this field are proposed. CONCLUSIONS This review highlights major challenges in attempting to extrapolate from the clear importance of gross corneal staining down to the meaning of observation of superficial punctate staining, and should promote greater circumspection in interpreting this phenomenon. The literature reflects that superficial punctate corneal staining does not reflect corneal injury or toxicity. More work is required to elucidate the various mechanisms underlying superficial punctate staining, and to provide clinicians with a rational interpretation algorithm for this observation.