Intravenous tissue plasminogen activator (IV-TPA), administered within 4.5 h of symptom onset, is the only therapeutic agent approved for achieving arterial recanalization in acute ischemic stroke. Current major guidelines recommend the use of a standard dose (0.9 mg/kg bodyweight; maximum 90 mg) of IV-TPA. However, comparable efficacy of IV-TPA was demonstrated in the observational studies from Japan when a lower dose (0.6 mg/kg bodyweight; maximum 60 mg) was used and later approved by the regulatory authorities. Although limited in numbers, considerable variations in the dose of IV-TPA are noted in recent publications from Asia, with variable results and optimal dose of TPA in Asia remains controversial. The authors present a systemic review of the existing literature and compare the efficacy and safety of standard-versus the low-dose IV-TPA therapy in acute ischemic stroke.