Tau protein is the major component of the intracellular filamentous deposits that define a number of neurodegenerative diseases. They include the largely sporadic Alzheimers disease, progressive supranuclear palsy, corticobasal degeneration, Picks disease and argyrophilic grain disease, as well as the inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Until recently, it was unclear whether the dysfunction of tau protein follows disease or whether disease follows the dysfunction of tau protein. The identification of mutations in Tau as the cause of FTDP-17 has resolved this issue by showing that the dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. About half of the known mutations have their primary effect at the protein level. They reduce the ability of tau protein to interact with microtubules and increase its propensity to assemble into abnormal filaments. Surprisingly, the other mutations have their primary effect at the RNA level, thus perturbing the normal ratio of three-repeat to four-repeat tau isoforms. Where studied, this resulted in the relative overproduction of tau protein with four microtubule-binding repeats in brain. Several Tau mutations give rise to diseases that resemble progressive supranuclear palsy, corticobasal degeneration or Picks disease. Moreover, the H1 haplotype of Tau has been shown to be a significant risk factor for progressive supranuclear palsy and corticobasal degeneration. At an experimental level, the work on FTDP-17 is rapidly leading to the development of good transgenic mouse models for the human tauopathies.