Pyroptosis, an inflammatory form of programmed cell death, plays a critical role in various neurological diseases. This review explores the molecular pathways of pyroptosis, including caspase-1-dependent and -independent routes, and highlights the role of the inflammasome machinery in initiating cell death. Key activators of pyroptosis include the NLR family, AIM2-like receptors, and the pyrin receptor family. The Gasdermin family, particularly GSDMD and GSDME, are executioner proteins involved in pyroptosis. Pyroptosis significantly impacts central nervous system (CNS) cells, including astrocytes, microglia, neurons, and the blood-brain barrier (BBB), contributing to the pathophysiology of neurological diseases. The review addresses pyroptosis in conditions such as HIV infection, drug abuse, Alzheimer's disease, and Parkinson's disease, emphasizing its connection to chronic inflammation and cell death. Pyroptosis is distinguished from other cell death mechanisms by its inflammatory characteristics and the release of proinflammatory cytokines. The review also discusses the role of pyroptosis in neuroinflammatory processes and its potential as a therapeutic target. Key findings include the involvement of NLRP1, NLRP3, and NLRP6 in pyroptosis, the role of AIM2 in recognizing dsDNA, and the function of the Pyrin-receptor family in inflammasome activation. The Gasdermin family, particularly GSDMD and GSDME, are central to pyroptosis, with their cleavage leading to membrane pore formation and the release of inflammatory mediators. The review also highlights the role of NINJ1 in plasma membrane rupture during pyroptosis. Overall, pyroptosis is a complex process with significant implications for neurological diseases, offering potential therapeutic avenues for mitigating these conditions.Pyroptosis, an inflammatory form of programmed cell death, plays a critical role in various neurological diseases. This review explores the molecular pathways of pyroptosis, including caspase-1-dependent and -independent routes, and highlights the role of the inflammasome machinery in initiating cell death. Key activators of pyroptosis include the NLR family, AIM2-like receptors, and the pyrin receptor family. The Gasdermin family, particularly GSDMD and GSDME, are executioner proteins involved in pyroptosis. Pyroptosis significantly impacts central nervous system (CNS) cells, including astrocytes, microglia, neurons, and the blood-brain barrier (BBB), contributing to the pathophysiology of neurological diseases. The review addresses pyroptosis in conditions such as HIV infection, drug abuse, Alzheimer's disease, and Parkinson's disease, emphasizing its connection to chronic inflammation and cell death. Pyroptosis is distinguished from other cell death mechanisms by its inflammatory characteristics and the release of proinflammatory cytokines. The review also discusses the role of pyroptosis in neuroinflammatory processes and its potential as a therapeutic target. Key findings include the involvement of NLRP1, NLRP3, and NLRP6 in pyroptosis, the role of AIM2 in recognizing dsDNA, and the function of the Pyrin-receptor family in inflammasome activation. The Gasdermin family, particularly GSDMD and GSDME, are central to pyroptosis, with their cleavage leading to membrane pore formation and the release of inflammatory mediators. The review also highlights the role of NINJ1 in plasma membrane rupture during pyroptosis. Overall, pyroptosis is a complex process with significant implications for neurological diseases, offering potential therapeutic avenues for mitigating these conditions.