The development of ischaemic brain damage depends on the severity and duration of the focal disturbance in cerebral blood flow. Several flow thresholds exist; if flow is decreased to a certain threshold there can be functional but potentially reversible impairment, while a decrease to lower thresholds results in morphological and therefore permanent damage. Tissue perfused at a value between these thresholds is termed the ‘penumbra’. This tissue has the potential for functional recovery if blood flow is re-established to a sufficient level within a limited time period, i.e. the ‘therapeutic window’.The existence of a therapeutic window for the restoration of blood flow is evident from experimental studies and clinical experience. It has formed the basis for the success of thrombolytic therapy (e.g. with alteplase) in ischaemic stroke if treatment is initiated within a short period (approximately 3 hours) after the onset of symptoms. Despite the success of thrombolytic therapy, additional strategies need to be developed for the treatment of ischaemic stroke. In particular, therapies that interrupt the molecular and biochemical alterations triggered during the ischaemic period and that continue after reperfusion would be beneficial. These biochemical changes may propagate ischaemic damage and contribute to the enlargement of infarcts.State-of-the-art imaging modalities, such as positron emission tomography and diffusion- and perfusion-weighted magnetic resonance imaging, demonstrate the presence of ischaemically compromised but viable tissue in patients who have had a stroke (and in animal models of focal ischaemia, in which the transient changes can be followed until the final state of infarction or recovery is reached). In selected groups of patients, therapeutic strategies, such as acute thrombolysis or the interruption of biochemical changes, can be evaluated using these imaging techniques, and the clinical course analysed in relation to effects on impaired perfusion and altered metabolism within ischaemic tissue.