The mechanism by which neurons die in human neurodegenerative diseases remains an enigma till today. Terminally differentiated neurons of normal brain are incapable of cell division. However, accumulating evidence has suggested that aberrant activation of the cell cycle in certain degenerative diseases leads to their demise. In Alzheimer's disease, regulators spanning every phase of the cell cycle are upregulated in affected neurons, leading to successful DNA replication, but unsuccessful mitosis. The end point of this nonproductive cycle of division is death. Elucidating the details of this cell cycle-mediated degenerative cascade may lead to novel strategies for curbing the onset and progression of degenerative diseases.