Rapid mobilization of leucocytes through endothelial and epithelial barriers is key in immune system reactivity. The underlying mechanisms that regulate these processes have been the basis for many recent studies. Traditionally, leucocyte extravasation had been believed to occur through a paracellular route, which involves localized disruption of endothelial cell junctions. However, more recently, a transcellular route has been described involving the passage through the endothelial cell body. Leucocytes are also able to migrate through epithelium to monitor mucosal tissues and microenvironments. A number of adhesion molecules are known to regulate transmigration of leucocytes through epithelial and endothelial layers. Paracellular and transcellular leucocyte transmigration are regulated by adhesion molecules such as PECAM-1 (platelet-endothelial cell adhesion molecule 1), CD99, VE-cadherin (vascular endothelial cadherin) and JAM (junctional adhesion molecule) proteins. The purpose of this review is to discuss the role of these molecules in leucocyte transmigration and how they contribute to the different mechanisms that regulate leucocyte trafficking.