The Semaphorins constitute a large family of secreted and membrane-tethered cell signaling molecules. They have functions in neural development, immunology, cardiac growth, vascular development, lung morphogenesis and axial bone patterning. Semaphorins are defined by the presence of a conserved Sema domain at the N-terminus. These proteins can be classified into eight classes depending on their structure and species origin. Classes 3 through 7 are found in vertebrates; class 3 are secreted, class 7 are GPI-anchored and class 4 through 6 are transmembrane proteins. Two distinct transmembrane receptor families have been identified as Semaphorin receptors. Neuropilins provide binding specificity for the class 3 Semaphorins, whereas Plexins, which also contain a Sema domain serve as signaling partners for class 3 Semaphorins and as functional receptors for transmembrane Semaphorins.