Leucocytes use sophisticated mechanisms to cross the endothelium lining the vasculature. This is initiated by chemokine-and adhesion molecule-induced intracellular signalling that controls adhesion, spreading, and motility. At the same time, adherent leucocytes trigger the endothelium, manipulating the barrier to promote their transmigration into the underlying tissues. Over the past years, our insights in the associated signalling events within the endothelium have increased considerably, albeit the order of events, their crosstalk, and the consequences for endothelial cells and leucocytes are only partially resolved. Here, we briefly review endothelial signalling that is initiated at the apical endothelial membrane, where the first contact with the leucocytes takes place and signal transduction is induced. In addition, we discuss subsequent events at endothelial cell-cell junctions insofar as they have been linked to transendothelial migration. Finally, we briefly touch upon the modulation of endothelial signalling by infectious pathogens, since these have developed additional, elegant ways to manipulate the endothelium and transendothelial migration that may provide new, relevant insights into this process.