Stroke kills 4.4 million individuals annually and is the most significant cause of somatic disability. Ultra-acute thrombolysis is the only proven specific medical therapy for stroke, but the pharmacoeconomic consequences of wide application of thrombolytic therapy have not been broadly reported. This review analyses available data on costs incurred by stroke morbidity and estimates how these might be influenced by thrombolytic therapy. These analyses are supported by: (i) estimated lifetime costs of stroke therapy (approximately $US60 000 per patient); (ii) a speculative example of thrombolytic therapy simulated in the setting of a comprehensive urban stroke centre; and (iii) recent data on the efficacy of thrombolysis in reducing disability. It is estimated that only 5% of acute stroke patients are eligible for thrombolysis, which prevents 1 case of long term disability among every 7 patients treated. It can be argued that the reduction in costs during the first year of medical therapy (e.g. rehabilitation, co-morbidity, nursing) due to successful thrombolysis is cancelled out by increased costs due to the associated investments (increased acute hospitalisations and neuroimaging, drug costs and potential complications). However, successful thrombolysis cuts all lifetime indirect costs (e.g, disability pensions, reduced income and productivity) and direct nonmedical costs (e.g. disability aids, domestic help), and significantly reduces lifetime dir ect medical costs (e.g. rehabilitation, stroke co-morbidity, nursing). In such a case, these savings are estimated to account for 84% of the total lifetime costs (approximately $US52 200). In our catchment area of 1 million individuals, the projected total savings in a simulated model of thrombolytic therapy would amount to 15 to 26% of the expenses budgeted for in-hospital therapy of the 800 patients with ischaemic stroke who are treated annually at our centre. Alternatively, the savings due to one successful thrombolysis cancel out the costs for the acute phase management of the number of patients needed to generate this nondisabled stroke survivor. Although those estimates are based on the use of thrombolysis in a well organised stroke care centre in an urban setting, where no substantial investments are necessary before full implementation of thrombolytic therapy can occur, it would seem advantageous to apply thrombolysis as widely as possible to reduce the economic burden of stroke. Since thrombolysis for ischaemic stroke is only well tolerated when administered by experienced clinicians in well established stroke centres, we encourage efforts to disseminate focused training programmes as well as investments in better organised stroke care worldwide. Globally, stroke is one of the leading medical causes of morbidity and mortality, and is a tremendous burden for healthcare systems around the world. Mortality due to stroke is second only to ischaemic heart disease, with 4.4 million individuals dying annually as the result of stroke (9% of all deaths).([1]) Stroke is the most significant cause of somatic disability. In the UK, even though the proportion of patients with stroke who are admitted to hospitals is among the lowest in Western countries,([2]) stroke still accounts for almost 5% of all health service costs, 7% of all hospital-bed days and 6% of all hospital costs.([3]) Novel acute-phase therapeutic options for stroke are becoming available. One such therapy is thrombolytic treatment using intravenous alteplase (recombinant tissue plasminogen activator). This has been investigated in 3 large international randomised controlled trials (RCTs).([4-6]) These studies demonstrated the efficacy of alteplase. For example, in the European study [European Cooperative Acute Stroke Study II (ECASS II)1,([5]) alteplase improved the likelihood of nondependent outcome by 8.3% at the expense of dependent outcomes, while mortality was not increased. One disadvantage of alteplase is that it can only be used in hospitals equipped with the medical technology associated with acute stroke care. To return the necessary investments in such equipment with a dividend, adoption of thrombolysis for stroke must be planned wisely. Therefore, attention is being focused on how the acute management of stroke should be organised, how large short term investments should be, and what the likely overall health economic implications stemming from these management modifications will be. These issues must be weighed against the decrease in stroke morbidity rates as well as changes in incidence of stroke as the population grows older. Furthermore, improved acute care is necessary to improve the functional outcome of the increasing number of stroke survivors. In the past, Western societies have allocated funds to investigate and institute the medically most effective therapies without rigorous consideration of their economic effectiveness (cost effectiveness), but this situation is rapidly changing. Cost-effectiveness analyses are becoming necessary for the treatments used for many disorders, and stroke is no exception. The use of data from these analyses is particularly important for developing countries, where healthcare funds and advanced medical technology are at a premium. The aim of this review is to gather information published on the economic impact and implications of thrombolytic therapy in stroke, and to project the actual cost effectiveness of this therapy by simulation in our own healthcare organisation as a model.