Activated glial cells (microglia and astrocytes) are a hallmark of several neurodegenerative disorders. A growing body of evidence supports the hypothesis that activation of glial cells by cytokines contributes to neurotoxicity. Although the precise mechanisms underlying glia-mediated neurotoxicity are unclear, it has been proposed that the generation of toxic free radicals or other neurotoxins is involved. This review focuses on the role of immune mediators released by activated glial cells in causing or preventing neuronal injury. Also, techniques used to assess neurotoxicity are discussed. It is hoped that research in this field will yield insights that will result in new therapies for neurodegenerative disorders.