Reperfusion of the ischemic brain parenchyma with intravenous thrombolysis and/or mechanical thrombectomy is the cornerstone of acute ischemic stroke treatment. A paradigm shift from “time is brain” to a more precision medicine approach now called “imaging is brain”, has taken place during the last decade. This transformation has been fueled by the progress in neuroimaging. Advanced Neuroimaging incorporates perfusion imaging in order to depict real-time cerebral perfusion disturbances and provide maps of the penumbra and ischemic core that will inform individualized clinical decisions. Advance neuroimaging has now a fundamental role in triaging patients that will receive reperfusion treatments beyond the conventional time windows of 4.5 hours for intravenous thrombolysis and 6 hours for mechanical thrombectomy. We provide a narrative review of all the pivotal observational studies and randomized-controlled clinical trials that supported the use of advance neuroimaging, as well as technical issues and pitfalls that may be useful for its implementation in routine clinical practice.