Use of intravenous tissue plasminogen activator (tPA) is one of the key elements of acute ischemic stroke management. Its use has not become widespread, and has faced significant problems in our country for more than a quarter of a century most probably due to many unanswered questions about issues related with daily practice. However, recent developments, which adequately focused and found solutions for most of these problems and questions, have led to a major change of point of view and understanding of the hyperacute management of stroke. This article, in the light of the relevant literature, discusses and provides clear recommendations for questions directed by neurologists practicing in Turkey mainly about typical neurologic issues faced in the setting of tPA use for acute stroke.