The inflammasome is a large macromolecular complex that contains multiple copies of a receptor or sensor of pathogen‐derived or damage‐derived molecular patterns, pro‐caspase‐1, and an adaptor called ASC (apoptotic speck containing protein with a CARD), which results in caspase‐1 maturation. Caspase‐1 then mediates the release of pro‐inflammatory cytokines such as IL‐1β and IL‐18. These cytokines play critical roles in mediating immune responses during inflammation and innate immunity. Broader studies of the inflammasome over the years have implicated their roles in the pathogenesis of a variety of inflammatory diseases. Recently, studies have shown that the inflammasome modulates neuroinflammatory cells and the initial stages of neuroinflammation. A secondary cascade of events associated with neuroinflammation (such as oxidative stress) has been shown to activate the inflammasome, making the inflammasome a promising therapeutic target in the modulation of neurodegenerative diseases. This review will focus on the pathogenic role that inflammasomes play in neurologic diseases such as Alzheimer's disease, traumatic brain injury, and multiple sclerosis. We here review the role of the inflammasome in the pathogenesis of traumatic brain injury (TBI). TBI is initiated by physical force exerted to head, resulting in neuronal injury and death. Primary insult is followed by a secondary cascade of events following neuroinflammation such as mitochondrial dysfunction, production of reactive oxygen species, potassium effluxes, and release of circulating DNA. These events can potentially trigger the activation of NLRP3, NLRP1, and AIM2 during TBI but have yet to be confirmed (dashed lines). NLRP3, NLRP1, and AIM2 associate with the adaptor protein ASC, which initiates the cleavage of pro‐caspase‐1 to the mature form of caspase‐1 which cleaves pro‐IL‐1β and pro‐IL‐18 into their mature forms of IL‐1β and IL‐18. We here review the role of the inflammasome in the pathogenesis of traumatic brain injury (TBI). TBI is initiated by physical force exerted to head, resulting in neuronal injury and death. Primary insult is followed by a secondary cascade of events following neuroinflammation such as mitochondrial dysfunction, production of reactive oxygen species, potassium effluxes, and release of circulating DNA. These events can potentially trigger the activation of NLRP3, NLRP1, and AIM2 during TBI but have yet to be confirmed (dashed lines). NLRP3, NLRP1, and AIM2 associate with the adaptor protein ASC, which initiates the cleavage of pro‐caspase‐1 to the mature form of caspase‐1 which cleaves pro‐IL‐1β and pro‐IL‐18 into their mature forms of IL‐1β and IL‐18. This article is part of the Special Issue “Neuroinflammation – A Two Way Street Directing CNS Injury and Repair”.