During the past decade, the concepts about the development and progression of neurodegenerative diseases, as well as of neurotoxic insults, have been completely revised mainly because of the recognition that most neurological disorders are the consequence of a complex relationship between glia and neurons. Following an insult to the CNS, glia becomes activated and releases new molecules not normally detectable in quiescent cells. Cytokines are among these molecules and have been implicated in the modulation of neurodegeneration. Here, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) contribute to neurodegeneration and the molecular mechanisms involved will be shortly reviewed.