The mechanism of plazminogen activation by streptokinase, tissue and urokinase-type plazminogen activators (PAs) were reviewed. The regulatory role of fibrin in plazminogen activation involving its direct interaction with tissue-type PA and indirect interaction with streptokinase and urokinase-type PAs was demonstrated. Recent information on the development of new PAs is also displayed. The result of studies of PA mutant derivatives synthesized by recombinant DNA techniques are discussed. Date on chimeric (hybrid) forms of Pas and their chemically synthesized conjugates are presented. The trend in search for Pas is analyzed. A new direction in the study of Pas for combined plazminogen activation and the further development of the methods of thrombolytic therapy was outlined.