Approximately 50% of patients hospitalized for stroke develop fever. In fact, experimental evidence suggests that high body temperature is significantly correlated to initial stroke severity, lesion size, mortality, and neurologic outcome. Fever occurring after stroke is associated with poor outcomes. We investigated the etiology of fever after stroke and present evidence evaluating the efficacy and safety of interventions used to treat stroke-associated fever. Oral antipyretics are only marginally effective in lowering elevated body temperature in this population and may have unintended adverse consequences. Nonpharmacologic approaches to cooling have been more effective in achieving normothermia, but whether stroke outcomes can be improved remains unclear. We recommend using body temperature as a biomarker and a catalyst for aggressive investigation for an infectious etiology. Care must be taken not to exceed the new standard of a maximum acetaminophen dose of 3 g/day to avoid patient harm.