The transcription factor nuclear factor-kappaB (NF-kappaB) is an ubiquitously expressed dimeric molecule with post-translationally regulated activity. Its role in the immune system and host defense has been well characterized over the last two decades. In contrast, our understanding of the function of this transcription factor in the nervous system (NS) is only emerging. Given their cytoplasmic retention and nuclear translocation upon stimulus, NF-kappaB members are likely to exert an important role in transduction of signals from synaptic terminals to nucleus, to initiate transcriptional responses. This report describes recent findings deciphering the diverse functions of NF-kappaB in NS development and activity, which range from the control of cell growth, survival and inflammatory response to synaptic plasticity, behavior and cognition. Particular attention is given to the specific roles of NF-kappaB in the various cells of the NS, e.g. neurons and glia. Current knowledge of the contribution of NF-kappaB to several neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's diseases is also summarized.