Eph receptor tyrosine kinases (Ephs) and their membrane-anchored ligands (ephrins) form a vital cell communication system capable of bi-directional signaling. This Eph receptor/ephrin system has classically been demonstrated to play a role in development. However, emerging evidence has revealed differential expression of Ephs and ephrins in numerous cancers. Recent studies suggest that this system influences invasive behaviour, promoting a more aggressive and metastatic phenotype. Hence, this minireview summarizes the current understanding of the contribution of both Eph receptors and their ephrin ligands to invasiveness in cancer, as well as their use as potential therapeutic targets.