In acute ischemic stroke, the volume of threatened but potentially salvageable tissue, i.e. the ischemic penumbra, is critical to the success of all acute therapeutic interventions, most notably thrombolysis. Despite the availability of both CT and MRI based techniques to detect and assess the penumbra, advanced imaging of this type remains under-utilized. Although the optimal selection criteria are still being refined and technical improvements are ongoing, rapid imaging of the penumbra appears to be the most promising approach to expanding the acute thrombolysis population, as well as tailoring treatment based on specific pathophysiological findings. This second article in a two-part series reviews current evidence for penumbral-based treatment selection and discusses the barriers to implementation of these advanced imaging techniques in acute stroke management protocols.