Polymorphonuclear neutrophils (PMN) play an important role in host defense and immune surveillance. However, PMNs can be detrimental when inflammatory stimuli are excessive and can lead to uncontrolled PMN adherence to microvascular endothelium, resulting in tissue and organ injury in the critically ill. The molecular basis of PMN-endothelial adherence is dependent on two groups of adhesion molecules and their co-specific ligands: the beta 2 integrins and their counterstructures, which are members of the immunoglobulin gene superfamily; and the selectins and their carbohydrate ligands expressed on vascular mucins and other glycoproteins or glycolipids. This review characterizes the events leading to PMN-endothelial adhesion and examines a number of in vivo models in which adhesion molecule blockade has protected against injury. The role of adhesion molecules in T-lymphocyte adhesion and immune surveillance of transplant allografts is also briefly discussed. The infectious risks of adhesion molecule blockade are reviewed.