Neuronal death occurs in various physiological and pathological processes, and apoptosis, necrosis, and ferroptosis are three major forms of neuronal death. Neuronal apoptosis, necrosis, and ferroptosis are widely identified to involve the progress of stroke, Parkinson’s disease, and Alzheimer’s disease. A growing body of evidence has pointed out that neuronal death is tightly associated with expression of related genes and alteration of signaling molecules. In addition, recently, epigenetics has been increasingly focused on as a vital regulatory mechanism for neuronal apoptosis, necrosis, and ferroptosis, providing a new direction for treating nervous system diseases. Moreover, growing researches suggest that histone methylation or demethylation is involved in the processes of neuronal apoptosis, necrosis, and ferroptosis. These researches may imply that studying the potential roles of histone methylation is essential for treating the nervous system diseases. Here, we review potential roles of histone methylation and demethylation in neuronal death, which may give us a new direction in treating the nervous system diseases.© 2023. The Author(s) under exclusive licence to University of Navarra.