Acute cerebral ischemia elicits an innate immune response that leads to a cascade of events that culminates in necrotic death of neurons and injury to their supportive structures in the neurovascular unit. Indeed, clinical studies have shown a close relationship between elevated levels of inflammatory markers and the risk for ischemic stroke. However, the signaling pathways that link these events are not well understood. A central regulator of inflammatory response is the transcription factor, nuclear factor‐kappa B (NF‐κB). The activation of NF‐κB is required for the transcriptional induction of many proinflammatory mediators involved in innate immunity, such as cellular adhesion molecules, cytokines, and growth factors. Therefore, factors that modulate the activity of NF‐κB could potentially regulate inflammatory processes in ischemic stroke. Here, we review the relationship between NF‐κB and ischemic stroke, its role in the neurovascular unit, and discuss some animal models that suggest that this relationship is causal.