The use of specific brain biomarkers might aid stroke diagnosis and that approach might permit rapid referral of stroke patients to hospitals with acute treatments, such as t-PA being available. Although thrombolytic therapy in acute stroke is effective since it accelerates clot lysis and earlier restoration of blood flow, many treated patients do not recanalize or do it too late and some suffer hemorrhagic transformations (HT) with high death rates. It has been recently described that biomarkers such as MMP-9 or fibronectin, might be used to select patients at higher risk of HT, and high PAI-1 that interferes with tPA-induced recanalization, might predict clot-lysis resistance and poor outcome. Moreover, high levels of MMP-9 and MMP-13 are involved in infarct growth in spite of thrombolytic therapy suggesting its ultra-early role in brain injury. Other biomarkers such as CRP may predict stroke mortality following reperfusion therapies. We will also show that the genetic background of stroke patients might condition plasma levels of some of those biomarkers and influence the therapeutic response in t-PA treated patients.