Several pieces of evidence suggest a role for polyamines in the regulation of plant vascular development. For instance, polyamine oxidase gene expression has been shown to be associated with lignification, and downregulation of S-adenosylmethionine decarboxylase causes dwarfism and enlargement of the vasculature. Recent evidence from Arabidopsis thaliana also suggests that the active polyamine in the regulation of vascular development is the tetraamine thermospermine. Thermospermine biosynthesis is catalyzed by the aminopropyl transferase encoded by ACAULIS5, which is specifically expressed in xylem vessel elements. Both genetic and molecular evidence support a fundamental role for thermospermine in preventing premature maturation and death of the xylem vessel elements. This safeguard action of thermospermine has significant impact on xylem cell morphology, cell wall patterning and cell death as well as on plant growth in general. This manuscript reviews recent reports on polyamine function and places polyamines in the context of the known regulatory mechanisms that govern vascular development.