Eph receptors and their membrane-bound ephrin ligands are developmental cell guidance cues that direct cell migration and orchestrate patterning processes by modulating adhesive or repulsive cell properties. During the past two decades, an exponentially growing interest in their function has resulted in a considerably advanced understanding of the cellular and molecular principles of Eph function in normal and oncogenic development. Ephs not only accurately guide the path of migrating cells, but also facilitate contact and communication between neighbouring cell populations, in particular at epithelial/mesenchymal boundaries. Precise cell positioning not only relies on accurately-graded expression of individual Eph/ephrin pairs, but on the sum of interactions within particular expression domains and their modulation through crosstalk with a range of other signalling systems. There is little doubt that Eph and ephrins provide exciting new targets for anti-cancer therapies, but in appreciation of the complexity of their signals and biological functions it is perhaps not surprising that the development of Eph-specific therapeutics is only emerging.