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Semaphorins are cell-membrane bound or secretory proteins that regulate cell migration, differentiation, proliferation, and morphology. Semaphorins are guidance cues that have either repulsive or attractive effects on growth cones and thus determine their direction toward or away from a target place. Moreover, they act as either chemorepellent or attractive molecules in other systems. Semaphorins were initially discovered as axon guidance molecules essential in nervous system development. However, growing evidence shows that they have a crucial role in other systems, including the immune, cardiovascular, and respiratory systems. This review highlights the immunoregulatory effects of semaphorin 3E in allergic airway inflammation.