The effect of core body and brain temperature on stroke outcomes has been addressed in many animal and human studies. From these, it is clear that elevated temperature worsens ischemic neuronal injury and that hypothermia may be neuroprotective. Based on these data, a few investigators have examined the role of fever prevention and induced hypothermia in the treatment of acute stroke patients. Since mechanical cooling techniques face inherent practical and safety problems, recent attention has been focused on pharmacological means. Specifically, a handful of studies have looked at whether acetaminophen is useful in preventing fever, or inducing hypothermia in stroke patients. These studies demonstrated only marginal effects on body temperature and none were sufficiently powered to address functional outcomes. In this review article, the rationale for acetaminophen therapy in acute stroke patients and the data regarding its potential though modest clinical role, will be discussed.