NF-kappaB is a transcription factor that regulates numerous physiological functions, and that is involved in the pathogenesis of various diseases. In the nervous system there is evidence supporting a dual role of NF-kappaB in neurodegenerative diseases; activation of NF-kappaB in neurons promotes their survival, whereas activation in glial and immune cells mediates pathological inflammatory processes. The reason for such a dichotomy lies in the complexity of the NF-kappaB system. Emerging research has begun to dissect the pathways leading to the activation of the different NF-kappaB proteins, and the gene targets of NF-kappaB, in cells of the nervous system. In this article the authors discuss recent findings concerning the roles of NF-kappaB in the pathogenesis of several neurodegenerative disorders, and its potential as a pharmaceutical target for these disorders.