•20-HETE acts in a feed forward mechanism with the renin-angiotensin system to perpetuate hypertension and vascular dysfunction.•20-HETE sensitizes smooth muscle to constrictor stimuli by inhibiting large conductance Ca2+-activated K+ channels and increasing Ca2+ entry through L-type Ca2+ channels.•20-HETE induces vascular remodeling through mechanisms independent of changes in blood pressure.•20-HETE enhances vascular inflammation and injury in diabetes and in models of ischemia/reperfusion and cerebrovascular oxidative stress.•20-HETE induces angiogenesis via increased production of reactive oxygen species (ROS). 20-HETE increases ROS though NADPH-oxidase and Rac1/2-dependent mechanisms and increased expression of VEGF and VEGFR2. 20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid that exhibits a myriad of biological effects in the vascular system. This review discusses the current knowledge related to the effects of 20-HETE on vascular reactivity, activation, and remodeling, as well as its role in vascular inflammation and angiogenesis. The information explaining how 20-HETE and the renin-angiotensin system interact to promote hypertension, vasoconstriction, and vascular dysfunction is summarized in this article. 20-HETE enhances vascular inflammation and injury in models of diabetes, ischemia/reperfusion, and cerebrovascular oxidative stress. Recent studies also established a role for 20-HETE in normal and pathological angiogenesis conditions. This review will also discuss the molecular mechanisms through which 20-HETE induces these vascular actions. Potential additional studies are suggested to address shortcomings in the current knowledge of 20-HETE in the vascular system.