Leukocyte transendothelial migration during homing and inflammation requires drastic cell morphological changes, involving cytoskeletal-directed clustering of adhesion receptors in specialized protrusive membrane structures in leukocytes and endothelial cells. Extravasation is an active process not only for leukocytes but also for endothelial cells, which promote the rapid and efficient entry of leukocytes to the target tissues, without disturbing the integrity of the endothelial barrier. Herein, we have revised the specialized protrusive structures (microvilli, endothelial docking structures, leukocyte lamellipodia and uropod) involved in the different stages of leukocyte extravasation. The adhesion receptor redistribution, cytoskeletal remodelling and intracellular signaling events that participate in this phenomenon are also discussed.