Recent research on Vitamin E (vit E) has pointed out novel mechanisms of action in addition to its well-known antioxidant activity. One of the main non-antioxidant actions of vit E is the modulation of intracellular signaling cascades. Vit E has been reported to directly or indirectly modulate different kinases such as protein kinase C (PKC), phosphatidylinositol-3-phosphate kinase (PI3K), glycogen syntase kinase-3B (GSK-3B), phosphatases such as protein phosphatase type 2A (PP2A), and key regulatory enzymes such as phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2). The neuroprotective effects attributed to vit E show complex mechanisms of action, in which its nonantioxidant activities are also playing a key role. In the present work, we have reviewed the effects of vit E in the intracellular signaling pathways in brain, focusing on its modulation of neuronal survival and growth, glial inflammatory response and vascular function. We will conclude with a note on the putative protective role of vit E in neurodegenerative processes.