Superoxide dismutases (SODs) are crucial antioxidant enzymes that play a significant role in protecting against oxidative stress, which is implicated in various cardiovascular diseases such as hypertension and atherosclerosis. There are three isoforms of SODs in mammals: cytoplasmic Cu/ZnSOD (SOD1), mitochondrial MnSOD (SOD2), and extracellular Cu/ZnSOD (SOD3). Each isoform has distinct subcellular locations and functions, contributing to compartmentalized redox signaling. SODs catalyze the conversion of superoxide anion (O$_2$•$^-$) to hydrogen peroxide (H$_2$O$_2$), which can further be reduced to water by other enzymes. SODs also inhibit the oxidative inactivation of nitric oxide (NO), preventing the formation of peroxynitrite and maintaining endothelial and mitochondrial function. The importance of each SOD isoform is highlighted by studies using genetically altered mice and viral-mediated gene transfer. While antioxidant therapies targeting SODs have shown promise, clinical evidence remains controversial. This review updates the roles of each SOD isoform in vascular biology, physiology, and pathophysiology, including atherosclerosis and hypertension. It also discusses the mechanisms by which SODs obtain catalytic metals and explores future therapeutic strategies based on SOD-dependent mechanisms.Superoxide dismutases (SODs) are crucial antioxidant enzymes that play a significant role in protecting against oxidative stress, which is implicated in various cardiovascular diseases such as hypertension and atherosclerosis. There are three isoforms of SODs in mammals: cytoplasmic Cu/ZnSOD (SOD1), mitochondrial MnSOD (SOD2), and extracellular Cu/ZnSOD (SOD3). Each isoform has distinct subcellular locations and functions, contributing to compartmentalized redox signaling. SODs catalyze the conversion of superoxide anion (O$_2$•$^-$) to hydrogen peroxide (H$_2$O$_2$), which can further be reduced to water by other enzymes. SODs also inhibit the oxidative inactivation of nitric oxide (NO), preventing the formation of peroxynitrite and maintaining endothelial and mitochondrial function. The importance of each SOD isoform is highlighted by studies using genetically altered mice and viral-mediated gene transfer. While antioxidant therapies targeting SODs have shown promise, clinical evidence remains controversial. This review updates the roles of each SOD isoform in vascular biology, physiology, and pathophysiology, including atherosclerosis and hypertension. It also discusses the mechanisms by which SODs obtain catalytic metals and explores future therapeutic strategies based on SOD-dependent mechanisms.