Adhesion molecules are necessary for leukocyte trafficking and differentiation. They serve to initiate cell-cell interactions under conditions of shear, and they sustain the cell-cell and cell-matrix interactions needed for cellular locomotion. They also can serve directly as signaling molecules activating pathways critical to cell functions, and they can act as accessory molecules maintaining cellular contacts necessary for signaling through other receptors. Given their critical role in the emigration of leukocytes into sites of inflammation, genetic mutations that thwart adhesion molecule expression or function can produce profound disruptions in host defense. Adhesion molecules might serve as therapeutic targets for inflammatory diseases.