Recanalization of acutely occluded arteries in the carotid territory, particularly the middle cerebral artery, by intra-arterial delivery of thrombolytic drugs, has advanced dramatically over the last decade. Randomized prospective studies have begun to show the potential impact of this form of intervention. Still, patient selection, therapeutic window, critical care support, and experience of the management team are clearly the determining features for the success of intra-arterial thrombolysis. The use of thrombolytic agents currently available, and research involving the next generation of these agents, open a field that shows promise for the improvement of outcomes of patients whose typical prognosis is poor.