Programmed cell death (PCD) is a form of regulated cell death distinct from accidental cell death (ACD) and is crucial for maintaining physiological homeostasis in mammals. PCD signaling cascades are tightly regulated to promote neuronal development, establish neural architecture, and shape the central nervous system (CNS). Abnormalities in PCD signaling cascades contribute to the irreversible loss of neuronal cells and function, leading to the onset and progression of neurodegenerative diseases (NDDs). This review summarizes the molecular processes and features of different modalities of PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and other novel forms of PCD, and their effects on the pathogenesis of NDDs such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. The review also discusses key factors involved in these PCD signaling pathways and explores potential therapeutic strategies targeting these pathways for the treatment of NDDs. Therapeutic approaches targeting the inhibition or facilitation of PCD signaling pathways offer promising clinical applications in treating NDDs.Programmed cell death (PCD) is a form of regulated cell death distinct from accidental cell death (ACD) and is crucial for maintaining physiological homeostasis in mammals. PCD signaling cascades are tightly regulated to promote neuronal development, establish neural architecture, and shape the central nervous system (CNS). Abnormalities in PCD signaling cascades contribute to the irreversible loss of neuronal cells and function, leading to the onset and progression of neurodegenerative diseases (NDDs). This review summarizes the molecular processes and features of different modalities of PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and other novel forms of PCD, and their effects on the pathogenesis of NDDs such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple sclerosis (MS), traumatic brain injury (TBI), and stroke. The review also discusses key factors involved in these PCD signaling pathways and explores potential therapeutic strategies targeting these pathways for the treatment of NDDs. Therapeutic approaches targeting the inhibition or facilitation of PCD signaling pathways offer promising clinical applications in treating NDDs.