Cerebral ischemia occurs due to the interruption of blood flow to the brain and can result in either temporary tissue dysfunction or permanent tissue infarction with a resultant variety of neurological deficits. The underlying etiology resulting in blood flow interruption and ischemia can be embolic, thrombotic, atheromatous vaso-occlusion or systemic hypotension. The initial ischemic insult incites a number of cellular and molecular cascades that can result in neuronal death, blood-brain barrier breakdown, neuroinflammation, and reperfusion injury, all of which contribute to the significant morbidity and mortality associated with ischemic stroke. In this chapter, we provide an overview of the pathophysiology underlying each of these processes.