Leukocyte inter actions with vascular endothelium are high lyorchestrated processes that include the capture of free-flow ing leukocytes from the blood with subsequent leukocyte rolling, arrest, firm adhesion, and ensuing diapedesis. These interactions occur under high shear stresses within venules and depend on multiple families of adhesion molecules. Many of the adhesion molecules involved are now identified. In addition, precise mechanisms underlying their regulation and our understanding of how different families of adhesion molecules work together is becoming clearer. Specifically, leukocyte/endothelial cell interactions such as capture, rolling, and firm adhesion can no longer beviewed asoccurring in discrete steps mediated by individual families of adhesion molecules, but rather as a series of overlapping synergistic interactions among adhesion molecules resulting in an adhesion cascade. Although long thought to be mediated by distinct adhesion pathways, overlapping adhesion cascades mediate normal lymphocyte recirculation to peripheral lymphoid tissues and inflammation-induced leukocyte migration. These cascades thereby direct leukocyte migration, which is essential for the generation of effective inflammatory responses and the development of rapid immune responses.