Ischemic stroke is a major public health problem worldwide. The potential to cure stroke patients with intravenous thrombolytic therapy has evolved to the use of intra-arterial thrombolytic agents. Fewer than 200 patients have been enrolled in randomized trials of intra-arterial therapy. In this article the authors have reviewed the literature listed in MEDLINE and EMBase, and searched relevant articles to examine the role of fibrinolytic agents in acute interventional stroke therapy. Only English language articles reporting five or more patients were included. Outcomes were defined at 90 days. Good outcome was defined on the modified Rankin Scale. Symtpomatic hemorrhage was defined as hemorrhage in the setting of clinical deterioration in the first 24 to 48 h. The search identified 57 studies of which 44 reported usable data. Only three randomized trials were reported. Of a total of 1140 patients, most (73%) were treated open-label with urokinase (Abbokinase, Abbott Laboratories). The best outcomes were reported in case series and slightly worse outcomes were reported in clinical trials. Overall, it was not possible to distinguish whether one agent was superior to the others. There is a paucity of published evidence on intra-arterial therapy for acute ischemic stroke. Alteplase (Activase, Genentech Inc.) is currently the drug of choice simply because it is available and it is the current intravenous standard. Further trials and developments are anticipated.