Sensorimotor gating, or the ability of a sensory event to suppress a motor response, can be measured operationally via prepulse inhibition (PPI) of the startle response. PPI is deficient in schizophrenia patients as well as other neuropsychiatric disorders, can be measured across species, and has been used widely as a translational tool in preclinical neuropharmacological and genetic research. First developed to assess drug effects in pharmacological and developmental models, PPI has become one of the standard behavioral measures in genetic models of schizophrenia and other neuropsychiatric disorders that exhibit PPI deficits. In this chapter we review the literature on genetic models of sensorimotor gating and discuss the utility of PPI as a tool in phenotyping mutant mouse models. We highlight the approaches to genetic mouse models of neuropsychiatric disease, discuss some of the important caveats to these approaches, and provide a comprehensive table covering the more recent genetic models that have evaluated PPI.