The semaphorins are a family of intercellular signaling proteins that has grown to include 19 identified members in higher vertebrates. Several of its members act as axonal guidance molecules. One participates in signaling in the immune system. The majority, however, do not yet have known biological functions. Recent studies have shown that neuropilins and plexins act as receptors for semaphorins. The most important challenge for the future is to define the biological roles of semaphorins in vivo.