Leukocyte adhesion to the endothelial cells lining the vessel wall and the subsequent migration of the leukocytes into the underlying tissue are key elements of both innate and adaptive immunity. Leukocyte extravasation is generally believed to take place through small gaps at intercellular endothelial cell junctions – the paracellular route. This view has, however, been repeatedly challenged by morphological studies demonstrating leukocyte migration through the endothelial cells themselves – the transcellular pathway. On the basis of the current experimental evidence, we propose consideration that both pathways are equally possible for a leukocyte's journey from the apical surface of the endothelium to its basal side.