Changes in cell proliferation seen in cancers initiated by adenomatous polyposis coli (APC) gene mutation are driven by the loss of an ability to negatively regulate the canonical WNT signalling pathway. However, mutant APC proteins also lack the ability to interact with a number of other ligands and it is possible that the loss of these interactions could contribute to the phenotype or to the development ofcolorectal tumours. One such association is with the microtubule plus-end binding protein EB1. Originally identified as an APC binding partner, EB1 is now known to be part of an evolutionarily conserved family of proteins involved in the regulation of microtubule dynamics and microtubule-dependent processes. Roles for the interaction between APC and EB1 have been identified in cellular functions as diverse as directed cell migration and mitosis, with potentially important implications for the behaviour of both normal epithelial cells and colorectal cancer cells. In this chapter our current understanding of the functional role of the APC-EB1 interaction will be reviewed.