Aims: To determine whether herpes simplex keratitis (HSK) has declined as an indication for penetrating keratoplasty (PKP) at the University of California San Francisco (UCSF) over the past 30 years. Methods: Records of the Hogan Eye Pathology Laboratory were reviewed to determine the incidence of PKP performed for HSK from 1972 through 2001. Archived corneal tissue with the diagnosis of HSK was evaluated for herpes simplex virus (HSV) DNA by polymerase chain reaction (PCR) based assays. Results: The number of corneal buttons submitted with the clinical diagnosis of HSK decreased from 1972 to 2001, while the overall number of PKPs performed did not. The percentage of corneal buttons with a clinical diagnosis of HSK that contained detectable HSV DNA did not change over the course of the study period. Conclusion: HSK declined as an indication for PKP from 1972 to 2001 at UCSF. It is unlikely that this decline was the result of improved diagnostic accuracy since detection of HSV DNA in corneal buttons with a clinical diagnosis of HSK was similar at the beginning and end of the study period.