Bidirectional signal transduction is a newly elucidated mechanism in intercellular communication. The bidirectional signal transduction mediated by the Eph-ephrin is an important representative in this field. The Eph family receptor tyrosine kinases and their membrane-bound ligands, the ephrins, play pivotal roles in the development of nervous system, angiogenesis, etc. The signal transduction into cells by Eph receptors is the forward signal, whereas the signal transduction by ephrins is the reverse signal. Based on their molecular structures, the ephrins can be divided into two subclasses, i.e. ephrinA and ephrinB. The ephrinBs are transmembrane proteins, which can activate FAK, JNK and Wnt signal transduction pathways through phosphotyrosine-dependent signaling and PDZ-binding motif-dependent signaling. The ephrinAs are glycosylphosphotidylinositol (GPI) anchored proteins, which can also mediate reverse signal transduction.