The use of tissue plasminogen activator in ischemic stroke is controversial. Many practicing physicians believe that its usefulness is established, while others, including professional specialty societies, are less sanguine. A review of the literature appears to show that the use of tissue plasminogen activator is efficacious and can result in highly improved outcomes for a majority of eligible patients. These findings may implicate important potential legal issues. Informed consent concerns and, potentially, medical malpractice claims may result, particularly in the context of evidence-based practice, pay for performance, and the currently limited use of tissue plasminogen activator for eligible patients.