Rapid progress in understanding the molecular basis of neurodegeneration has been tightly linked with recent discoveries in the field of programmed cell death (PCD). Analysis of PCD in neuronal demise has led to identification of several associated phenomena, such as re-initiation of the cell cycle and the key role of oxidative stress, although putative causal relationships between these events are still debatable. These issues are reviewed here in the context of acute and chronic neurodegenerative processes. In addition, newly emerging concepts concerning cell-cycle re-initiation are discussed in terms of their potential impact on the development of more effective therapeutic strategies.