The fundamental importance of the concept of the ischemic penumbra is the recognition that ischemic processes may be reversible. Although founded on the concept of critical changes of blood flow, the ischemic penumbra can also be described in molecular terms. A molecular delineation of the ischemic core employs analyses of appropriate proteins, many of which have a short half-life and hence rapid reductions in concentration. Multitracer PET imaging with 15O allows generation of quantitative brain maps for CBF, CMRO2, OEF, cerebral blood volume (CBV), and regional cerebral metabolic rate of glucose. Evolving MRI techniques are useful for assessment of penumbral tissue in acute stroke. DWI is increasingly available in the setting of acute stroke, and for rapid acquisition it is performed using echoplanar magnetic resonance imaging methods. The blood oxygen level dependent (BOLD) technique has been used to differentiate perfused and non-perfused tissues during experimental ischemia in cats.