The activity of integrins on leukocytes is tightly controlled, and their adhesion capacity shifts rapidly when cells emigrate from the blood to the tissues. The leukocyte-specific β2 integrin LFA-1 (αLβ2) is the most important integrin expressed by leukocytes that regulate lymphocyte migration and the initiation of an immune response through binding to ICAM-1,-2 or-3. The binding activity of LFA-1 is rapidly altered by intracellular stimuli that activate LFA-1. Although alterations in the affinity of LFA-1, which leads to enhanced ICAM-1 binding, have been proposed, evidence is emerging that dynamic reorganisation of LFA-1 into microclusters is the major mechanism that regulates its binding capacity.