The penumbral concept is defined as different areas within the ischemic region evolve into irreversible brain injury over time and that this evolution is most critically linked to the severity of the decline in cerebral blood flow (CBF). The ischemic penumbra was initially defined as a region of reduced CBF with absent spontaneous or induced electrical potentials that still maintained ionic homeostasis and transmembrane electrical potentials. The reduction of CBF levels to between 10 and 15 mL/100 g/min and approximately 25 mL/100 g/min are likely to identify penumbral tissue, and the ischemic core of irreversible ischemic tissue has a CBF value below the lower threshold. The role of identifying this critically deprived brain tissue from CBF in triaging patients for endovascular ischemic therapy is evolving. In this review we focus on the basic science of the penumbral concept and identification using various imaging modalities (PET, MRI, and CT) in animal models and human studies. Another article in this supplement addresses the clinical implication and the current understanding and application of this concept into clinical practice of endovascular ischemic stroke therapy.