Blood vessels express 3 isoforms of superoxide dismutase (SOD): cytosolic or copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD) localized in mitochondria, and an extracellular form of CuZn-SOD (EC-SOD). Because there are no selective pharmacological inhibitors of individual SOD isoforms, the functional importance of the different SODs has been difficult to define. Recent molecular approaches, primarily the use of genetically-altered mice and viral-mediated gene transfer, have allowed investigators to begin to define the role of specific SOD isoforms in vascular biology. This review will focus mainly on the role of individual SODs in relation to endothelium under normal conditions and in disease states. This area is important because reactive oxygen species and superoxide anion are thought to play major roles in changes in vascular structure and function in pathophysiology.