The semaphorin family are soluble and membrane-bound proteins originally identified as axon guidance factors which are involved in the development of the neuronal system. Moreover, Plexin family members are the most representative semaphorin receptors. Recently, accumulating evidence indicates that several semaphorins, so-called 'immune semaphorins' such as Sema3A, 3E, 4A, 4D, 6D, 7A are crucially involved in various phases of immune responses. Some semaphorins and their receptors regulate immune cell activation or differentiation, whereas others navigate the trafficking of immune cells. Here, we review the current knowledge of the function of semaphorins and their corresponding receptors in immune system, which is focused on dendritic cell, T cell, macrophage, and osteoclast.