Intravenous thrombolysis with rt-PA is effective in acute stroke patients [304, 305]. Although tPA is the only proven therapy for acute stroke, only 3% to 4% of all stroke patients are currently treated [251]. The limited use of rt-PA is partly due to safety concerns of neurologists, internal medicine and emergency physicians [21, 170] and the narrow therapeutic time window. The extension of the therapeutic window would be an important step towards a broader application. It has been argued that the selection of stroke patients likely to respond to thrombolysis might improve functional outcome within the 3 h time window and extend the window towards 6 hours after stroke onset [2, 131]. In this chapter we discuss, how stroke MRI can be used to guide acute therapy especially whether to give or withhold thrombolytic therapy. In essence, the presence of a vessel occlusion according to MRA is associated with a PWI/DWI-mismatch, the stroke MRI setting that defines the ideal candidate for thrombolysis [281, 307]. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.