There is still a lack of pharmacological treatment options for traumatic brain injury (TBI), the dominant cause of death and disability in persons under the age of 40 in the developed part of the world. Clinical TBI is a markedly complex disease, categorized into different subtypes that differ in their pathophysiology, treatment requirements, and long-term consequences. For successful development of novel treatment options, refined preclinical evaluation in rodent TBI models is mandatory. Since persisting cognitive deficits, impaired motor function, depression, and personality changes are common sequelae in TBI patients, preclinical models must produce clinically relevant behavioral deficits. Additionally, clinical TBI is a markedly heterogeneous disease with a severity span from immediately fatal to mild injuries with minor and passing symptoms. Ideally, a rodent TBI model should thus be adjustable in terms of injury severity. One of the most widely used rodent TBI model is the fluid percussion injury (FPI), which meets many of the criteria for a clinically relevant experimental model. The FPI technique relies on a fluid pressure pulse being transmitted into the skull cavity of the animal, allowing for a degree of brain displacement. By placing the craniectomy and the injury site either over the midline of the skull (the central FPI; cFPI) or over one hemisphere (the lateral FPI; lFPI) the injury shows either more diffuse (cFPI) or more focal (lFPI) characteristics. Although FPI has many advantages over other TBI models, including the possibility to vary important injury characteristics, the outcome after TBI may be influenced by other features such as gender, age, species, and even strain which should be considered in the design of the rodent models. In this chapter, we discuss the limitations and advantages, as well as the special considerations necessary when using the FPI model in rodents.