Review of results of experimental and clinical studies indicates that the area of physiologically impaired, but potentially salvageable, tissue surrounding the central core of focal cerebral ischemia that develops shortly after onset of vessel occlusion is complex and dynamic with severity and duration thresholds for hypoxic stress and injury that are specific to tissue site, cell type, molecular pathway or gene expression investigated, and efficiency of collateral or residual flow and reperfusion. Identification of this ischemic penumbra in the acute stroke clinical setting is an important goal for stroke researchers and clinicians. Recent advances in neuroimaging allowed a better understanding of this physiopathological process. However, there is not a perfect penumbra imaging technique and each one has its own advantages and disadvantages. Numerous thrombolytic and potentially neuroprotective agents have been studied in stroke patients, with little success, as the only approved therapy is thrombolysis with recombinant tissue plasminogen activator within 3 h of stroke onset in highly selected patients (<10% of all acute stroke patients in some specialized centers). One major obstacle in the development of effective therapies for ischemic stroke has been the lack of versatile imaging techniques. The development of penumbra concept and its detection through modern cerebral image techniques can extend the patients' selection for thrombolysis. A number of multicenter clinical trials are now under way to test these models and confirm the utility of penumbra imaging for treatment decisions. Present knowledge about visualization of the salvageable penumbra suggests a promising future in which penumbra imaging studies are performed routinely in the acute stroke setting and the data provided by these studies assist in individualizing therapeutic decisions and identifying effective therapies that can be delivered at late time points. So, the main target of management is 'penumbra', or salvageable tissue, which is primarily dependent upon the expediency of the whole process, better expressed by the phrase 'Penumbra (and not Time) is Brain'.