Acute thrombolysis has a proven benefit for adults presenting with acute ischemic stroke, but data within the pediatric population are extremely limited. We report the case of a 14-year-old girl who presented with right-sided weakness and ataxia, loss of sensation, and altered mental status. Magnetic resonance imaging with diffusion-weighted imaging showed an acute lesion in the distribution of the left posterior cerebral artery, and magnetic resonance angiogram demonstrated occlusion of the third branch of the left posterior cerebral artery. With parental consent, clinicians decided to infuse an adult dose of weight-adjusted intravenous alteplase at 3.5 hours from onset of symptoms, with subsequent improvement in National Institutes of Health Stroke Scale score from 11 to 3. Computed tomography angiogram at 24 hours showed recanalization of the occluded vessel with no evidence of intracranial hemorrhage. Stroke Scale score at discharge was 3, with modified Rankin Scale scores at discharge of 1 and at 90 days of 0. This case highlights the importance of magnetic resonance imaging in diagnosing pediatric acute ischemic stroke and suggests consideration of thrombolysis in select confirmed pediatric stroke cases. However, a rigorous evidence base is lacking, and clinical trials have not been successful in recruiting patients.