Alteplase for acute ischemic stroke may be the first stroke intervention to have a significant public health impact. In February 1999, this therapy was conditionally licensed in Canada for acute ischemic stroke within three hours of symptom onset. However, considerable controversy exists regarding its safety, its wider applicability outside clinical trials, and its ultimate availability. In this article we review the thrombolytic literature, attempt to answer many of the concerns, provide new guidelines for its use, and cite the need for more information about whom we should and should not be treating with this therapy.