Current treatment protocols using reperfusion therapy for acute ischemic stroke rely on non-contrast computed tomography (NCCT), with most indications including the absence of acute hemorrhage or large volume of infarction in the presence of clinical signs and symptoms. This predictably results in a significant incidence of the administration of reperfusion therapy to patients with "stroke mimics," such as migraine headache or Todd's paralysis after a seizure. Diffusion-weighted imaging (DWI) is a technique based on magnetic resonance imaging (MRI) that may be more sensitive and specific for acute cerebral ischemia than NCCT. In addition, data for techniques such as perfusion-weighted imaging can be acquired with minimal additional time required. This may allow better risk assessment of a clinical response to reperfusion therapy vs. the possibility of hemorrhagic complications. This article describes a methodical review of studies comparing the sensitivity, specificity, positive predictive value, and negative predictive value of DWI vs. NCCT in the evaluation of acute ischemic stroke. Data from studies meeting our screening criteria are combined to produce overall values for each.