The protein tau is the most abundant microtubule associated protein in the central and peripheral nervous system. In the brain, tau plays a role in the assembly and stabilization of microtubules. The function of tau, however, appears to overlap with other microtubule binding proteins. The observation that tau is associated with neurodegenerative diseases has renewed interest in this protein. Various aspects of structure and biochemistry of tau, fibril formation and clinical perspectives, including therapeutic strategies are reviewed in this chapter.