The startle is a relatively simple ubiquitous reflex. Interestingly, it has a "non-zero baseline", i.e., its magnitude can be reduced or enhanced. We reflect here on the translational value of prepulse inhibition and fear-related potentiation as endophenotypes that can be used for the investigation of complex psychiatric diseases such as schizophrenia and anxiety-related disorders. Our main conclusions are that both phenomena of startle modulation are useful tools for basic research in investigating the genetic and/or neurobiological basis of certain aspects of these disorders. Because of their stable and robust nature, however, both biomarkers are of limited use for predicting the occurrence of diseases in high-risk people or for predicting the course of an illness.