Eph receptors and ephrins have captured the interest of the developmental biology community in recent years for their pleiotropic functions during embryogenesis. Loss-of-function studies using various animal models have demonstrated the involvement of Ephs and ephrins in many aspects of embryogenesis including segmentation, neural crest cells migration, angiogenesis, and axon guidance. An essential property of this signaling pathway is the ability of both Ephs and ephrins to behave as receptors or ligands and their consequent cell autonomous and nonautonomous mode of action. While many reports did not discriminate between Eph autonomous signaling (forward) and ephrin autonomous signaling (reverse), recent genetic and in vivo studies have shown that both forward and reverse signaling play important roles during embryogenesis.