Research models of traumatic brain injury (TBI) hold significant validity towards the human condition, with each model replicating a subset of clinical features and symptoms. After 30 years of characterization and implementation, fluid percussion injury (FPI) is firmly recognized as a clinically relevant model of TBI and the hallmarks of TBI in man can be faithfully reproduced. Variations in the surgical procedure provide the ability to induce focal, diffuse, or mixed focal and diffuse brain injury in various laboratory species. Being fully scalable, fluid percussion can induce mild, moderate, or severe brain injury in subjects of either sex, at any age. This chapter outlines the procedures for FPI in adult male rats and mice. With these procedures, it becomes possible to generate brain-injured laboratory animals for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be evaluated.