The semaphorin family consists of soluble and membrane-bound proteins originally identified as axonal guidance cues functioning during neuronal development. However, it is becoming increasingly clear that semaphorins play diverse roles in organogenesis, vascular growth, and tumor progression. In addition, emerging evidence indicates that several semaphorins, called "immune semaphorins," play crucial roles also during immune responses. Extensive studies on the immune semaphorins have revealed not only parallels but also differences in the semaphorin functions between the immune and nervous systems, providing unexpected but meaningful insights into the biological activities of these molecules. This chapter focuses on our current understanding of the roles of semaphorins and their receptors in the immune system.