Vascular inflammation underlies most forms of cardiovascular disease, which remains a prevalent cause of death among the global population. Advances in the biology of neutrophils, as well as insights into their dynamics in tissues, have revealed that these cells are prominent drivers of vascular inflammation though derailed activation within blood vessels. The development of powerful imaging techniques, as well as identification of cells and molecules that regulate their activation within vessels, including platelets and catecholamines, has been instrumental to better understand the mechanisms through which neutrophils protect or damage the organism. Other advances in our understanding of how these leucocytes exert detrimental functions on neighbouring cells, including the formation of DNA-based extracellular traps, constitute milestones in defining neutrophil-driven inflammation. Here, we review emerging mechanisms that regulate intravascular activation and effector functions of neutrophils, and discuss specific pathologies in which these processes are relevant. We argue that identification of pathways and mechanisms specifically engaged within the vasculature may provide effective therapies to treat this prevalent group of pathologies.