A reduction in neuronal damage following acute ischaemic stroke can be achieved by two major strategies: restoration of cerebral blood flow through the use of thrombolytics, and inhibition of the pathophysiological cascade that occurs as a result of a decreased cerebral blood flow through the use of neuroprotective agents. Therefore, combination therapy with thrombolytic and neuroprotective agents may provide additional benefits to those that can be achieved using the individual agents alone. Indeed, such benefits have already been demonstrated in several animal studies. However, a number of problems in trial design and statistical methodology need to be overcome. Nevertheless, combination therapy offers the potential of reducing the cost of stroke in terms of both health care and social welfare, and as well as limiting disability.