Background <p>Regulation of vascular endothelial permeability is crucial for maintaining hemostasis and controlling extravasation of immune cells in response to injury or infection. A transient increase in vascular permeability is a vital response to inflammation, allowing neutrophils to invade the inflamed tissue and clear the pathogen.</p> Findings <p>The close interaction between neutrophils and the activated, inflamed endothelium, followed by leukocyte trafficking across the endothelial layer, can, however, also contribute to maladaptive vascular hyperpermeability. This increased permeability allows plasma proteins and fluid to escape into the surrounding tissue, leading to edema, a hallmark and frequent complication of many inflammatory disorders. Neutrophils also contribute to the resolution of inflammation by restricting further neutrophil recruitment through chemokine degradation, the formation of neutrophil extracellular traps (NETs), and by promoting their own apoptosis via the release of pro-apoptotic microparticles. Neutrophils, therefore, also contribute to the regulation of vascular permeability and to the restoration of tissue homeostasis in inflammatory conditions.</p> Implications <p>This review summarizes the known mechanisms by which neutrophils regulate acute and chronic vascular permeability in autoimmune and non-autoimmune inflammatory diseases, and highlights the potential translational implications. Finally, we discuss overlapping and distinct mechanisms in neutrophil trafficking and vascular permeability.</p>