The tubulin molecule is unusual because of the number and nature of post-translational modifications that it undergoes. These modifications may be involved in regulating microtubule stability and interactions with microtubule-associated proteins, but they also may have as yet undiscovered functions. Certain of these modifications are found in many other proteins; these include phosphorylation of a serine residue in β-tubulin and acetylation of a lysine residue in α-tubulin. Other modifications occur exclusively, or almost exclusively in tubulin. Among these are the removal and addition of a tyrosine at the C-terminus of α and the addition of several glutamate or glycine residues to the γ-carboxyl group of glutamate residues in the C-terminal regions of both α and β. The identification of the mechanisms by which these modifications occur and of their roles in microtubule assembly and function are currently very active topics of research; they will be addressed in this chapter.