NF-kappaB is a well-characterized transcription factor with multiple physiological and pathological functions. NF-kappaB plays important roles in the development and maturation of lymphoids, regulation of immune and inflammatory response, and cell death and survival. The influence of NF-kappaB on cell survival could be protective or destructive, depending on types, developmental stages of cells, and pathological conditions. The complexity of NF-kappaB in cell death and survival derives from its multiple roles in regulating the expression of a broad array of genes involved in promoting cell death and survival. The activation of NF-kappaB has been found in many neurological disorders, but its actual roles in pathogenesis are still being debated. Many compounds with neuroprotective actions are strongly associated with the inhibition of NF-kappaB, leading to speculation that blocking the pathological activation of NF-kappaB could offer neuroprotective effects in certain neurodegenerative conditions. This paper reviews the recent developments in understanding the dual roles of NF-kappaB in cell death and survival and explores its possible usefulness in treating neurological diseases. This paper will summarize the genes regulated by NF-kappaB that are involved in cell death and survival to elucidate why NF-kappaB promotes cell survival in some conditions while facilitating cell death in other conditions. This paper will also focus on the effects of various NF-kappaB inhibitors on neuroprotection in certain pathological conditions to speculate if NF-kappaB is a potential target for neuroprotective therapy.