Acute stroke is a common presentation to emergency departments and is the third leading cause of death in the United States. Despite the frequency of this event, and its substantial morbidity and mortality, few therapies exist to limit the damage from this devastating diagnosis. One pharmacotherapy for ischemic stroke that has demonstrated efficacy in this setting is tissue plasminogen activator (Activase; tPA; alteplase). Current guidelines for this agent recommend its use within the first 3 hr of the onset of stroke symptoms in patients who meet specified criteria. However, more recent data have lead to recommending the extension of this time frame to 4.5 hr after onset of symptoms in specific patient populations. Although this therapy has demonstrated efficacy in improving outcomes, its use is often complicated by complex inclusion and exclusion criteria, risk of hemorrhage, requirement for intense patient monitoring, substantial cost, and the potential for devastating medication errors.