Septins are an evolutionarily conserved family of genes that encode a P loop-based GTP-binding domain flanked by a polybasic domain and (usually) a coiled-coil region. They have roles in cytokinesis, vesicle trafficking, polarity determination, and can form membrane diffusion barriers, as well as in microtubule and actin dynamics. Septins can form hetero-oligomeric complexes and possibly function as dynamic protein scaffolds. Recently, it has been shown that there are at least 13 human septin genes that exhibit extensive alternate splicing. There are complex patterns of human septin gene expression and recently it has been found that alterations in septin expression are seen in human diseases including neoplasia. This review summarises the essential properties of septins and outlines the accumulating evidence for their involvement in human neoplasia. Septins may belong to the class of cancer critical genes where alteration in expression profile (including alterations in the spectrum of transcripts expressed) may underpin their role in neoplasia as opposed to specific mutational events.