It is likely that thrombolytic agents will play a role in the management of acute ischemic stroke in well-selected patients, intravenous administration is most practicable. However, intra-arterial administration via superselective catheterization is an alternative option that may offer advantages is certain settings (e.g., angiography suite, intraoperatively). Tissue plasminogen activators appear safer than streptokinase. Fibrinolytic agents offer the unproven potential for improving stroke outcome with less risk of intracranial bleeding. LMWHs can be administrated subcutaneously with minimal blood monitoring. These agents may prove more useful for secondary stroke prevention rather than acute treatment. Introduction of other agents like monoclonal antibodies directed against leukocyte adhesion molecules, aspirin, or ticlopidine offer other potential approaches to improving stroke outcome.