Neurofibrillar protein aggregates containing tau are one of the major hallmarks of Alzheimer's disease (AD). In normal cells, tau stabilizes axonal microtubules, which are the tracks for intracellular traffic. In AD, tau becomes abnormally phosphorylated, aggregates into paired helical filaments and loses its ability to maintain the microtubule tracks. There is renewed interest in tau as a causative factor in neurodegenerative disease based on recently discovered mutations in the gene encoding tau. This article discusses how changes in tau protein could lead to retraction of neuronal processes and thus cell death and argues that tau pathology, rather than beta-amyloid, might be the most reliable indicative factor for AD.