Pyroptosis, an inflammatory form of programmed cell death, has gained significant attention for its role in various neurological diseases. This review explores the molecular signaling pathways governing pyroptosis, including caspase-1-dependent and independent routes, and the critical role of inflammasomes in initiating cell death. The Nucleotide-binding domain leucine-rich repeat (NLR) containing protein family, Absent in melanoma 2-like receptor family, and Pyrin receptor family are essential activators of pyroptosis. The Gasdermin family, particularly GSDM, is a key executioner protein in pyroptosis, leading to membrane rupture and the release of proinflammatory cytokines. Pyroptosis plays a significant role in the pathophysiology of various central nervous system (CNS) cell types, including astrocytes, microglia, neurons, and the blood-brain barrier (BBB). The review also examines the involvement of pyroptosis in specific neurological conditions such as HIV infection, drug abuse, Alzheimer's disease, and Parkinson's disease. By understanding the intricate connections between pyroptosis, chronic inflammation, and cell death, the review provides valuable insights into potential therapeutic targets for mitigating these complex conditions.Pyroptosis, an inflammatory form of programmed cell death, has gained significant attention for its role in various neurological diseases. This review explores the molecular signaling pathways governing pyroptosis, including caspase-1-dependent and independent routes, and the critical role of inflammasomes in initiating cell death. The Nucleotide-binding domain leucine-rich repeat (NLR) containing protein family, Absent in melanoma 2-like receptor family, and Pyrin receptor family are essential activators of pyroptosis. The Gasdermin family, particularly GSDM, is a key executioner protein in pyroptosis, leading to membrane rupture and the release of proinflammatory cytokines. Pyroptosis plays a significant role in the pathophysiology of various central nervous system (CNS) cell types, including astrocytes, microglia, neurons, and the blood-brain barrier (BBB). The review also examines the involvement of pyroptosis in specific neurological conditions such as HIV infection, drug abuse, Alzheimer's disease, and Parkinson's disease. By understanding the intricate connections between pyroptosis, chronic inflammation, and cell death, the review provides valuable insights into potential therapeutic targets for mitigating these complex conditions.