The process of leukocyte emigration from the blood into a site of inflammation can be dissected into four distinct but continuous stages involving sequential interactions of different adhesion molecules on the leukocyte and endothelial surfaces. Although the molecules mediating adhesion to the luminal surface have been well studied, much less is known about the final stage of this process, transendothelial migration. This is the stage in which a leukocyte bound to the vascular wall passes between adjacent endothelial cells; it is a complex process in its own right, involving continuous structural, mechanical, and biochemical changes in both interacting cell types. Distinct cell adhesion molecule and signal transduction mechanisms that appear to be involved in this phase are discussed here.