Eph receptor tyrosine kinases (Ephs) and their membrane anchored ephrin ligands (ephrins) form an essential cell-cell communication system that directs the positioning, adhesion and migration of cells and cell layers during development. While less prominent in normal adult tissues, there is evidence that up-regulated expression and de-regulated function of Ephs and ephrins in a large variety of human cancers may promote a more aggressive and metastatic tumour phenotype. However, in contrast to other RTKs, Ephs do not act as classical proto-oncogenes and do not effect cell proliferation or differentiation. Mounting evidence suggests that Eph receptors, through de-regulated re-emergence of their mode of action in the embryo may direct cell movements and positioning during metastasis, invasion and tumour angiogenesis. This review discusses these and other emerging roles of Eph receptors during oncogenesis.