Neutrophils are the first cell type to arrive at the injury sites and play a critical role in host defense, by virtue of its ability to adhere and transmigrate through endothelium, to phagocytose foreign pathogens, and to produce free oxygen radicals and proteolytic enzymes. Yet, inappropriate neutrophil activation causes tissue damage and various inflammatory diseases. These physiological and pathological functions of neutrophils depend on the engagement of certain surface receptors, especially α M β 2, the major β 2 integrin receptor present on neutrophil surface. Understanding of the molecular mechanisms underlying ligand binding by α M β 2, as well as the roles of α M β-ligand interactions in neutrophil functions will enable us to regulate more precisely neutrophil activities: that is, to promote their host defense functions, and at the same time to minimize their deleterious effects on normal cells.