The CRMP Family of Proteins and Their Role in Sema3A Signaling -- GTPases in Semaphorin Signaling -- Intracellular Kinases in Semaphorin Signaling -- MICAL Flavoprotein Monooxygenases: Structure, Function and Role in Semaphorin Signaling -- Signaling of Secreted Semaphorins in Growth Cone Steering -- Modulation of Semaphorin Signaling by Ig Superfamily Cell Adhesion Molecules -- Proteoglycans as Modulators of Axon Guidance Cue Function -- Semaphorin Signals in Cell Adhesion and Cell Migration: Functional Role and Molecular Mechanisms -- Semaphorin Signaling During Cardiac Development -- Semaphorin Signaling in Vascular and Tumor Biology -- Semaphorin Signaling in the Immune System. Since the identification of the first two semaphorins in the early 1990s, Se- la (Fasciclin IV) and Sema3A (collapsin), more than 25 semaphorin genes have been described. Although originally identified as repulsive guidance signals for extending axons, these secreted and membrane-associated glycoproteins are extremely pleiotropic, and many serve diverse roles unrelated to axon guidance. These include multiple distinct roles within a given biological system or tissue, including axon guidance, cell migration and neuronal apoptosis in the nervous system, and also parallel functions in seemingly disparate systems, such as cell migration in the nervous, cardiovascular and immune systems. Our knowledge of the cellular actions of semaphorin family members has advanced significantly over the past several years, and the receptors and intracellular signaling mechanisms that underlie semaphorin function are being unveiled at a rapid pace. Although plexins are the predominant family of semaphorin receptors, multiple (co-)receptor proteins function in several semaphorin signaling events. A unifying principle that defines the function of high-affinity semaphorin receptors characterized to date is their multimeric character. Unrelated receptor proteins with distinct functions (e. g. , ligand-binding, signal-transducing, modulatory) are assembled into large holoreceptor complexes to detect and respond to semaphorin proteins present in the extracellular space. There is a growing appreciation that the composition of a semaphorin receptor complex not only determines ligand specificity and sensitivity but also dictates the functional outcome of a ligand-receptor interaction.