As a principal neuronal microtubule-associated protein, tau has been recognized to play major roles in promoting microtubule assembly and stabilizing the microtubules and to maintain the normal morphology of the neurons. Recent studies suggest that tau, upon alternative mRNA splicing and multiple posttranslational modifications, may participate in the regulations of intracellular signal transduction, development and viability of the neurons. Furthermore, tau gene mutations, aberrant mRNA splicing and abnormal posttranslational modifications, such as hyperphosphorylation, have also been found in a number of neurodegenerative disorders, collectively known as tauopathies. Therefore, changes in expression of the tau gene, alternative splicing of its mRNA and its posttranslational modification can modulate the normal architecture and functions of neurons as well as in a situation of tauopathies, such as Alzheimer's disease. The primary aim of this review is to summarize the latest developments and perspectives in our understanding about the roles of tau, especially hyperphosphorylation, in the development, degeneration and protection of neurons.