Reactive oxygen species (ROS) are known participants in several cellular processes. Superoxide anion radical, one example of ROS, forms as a result of normal cellular respiration and is usually cleared successfully by superoxide dismutase (SOD) and other radical scavengers. However, when superoxide exceeds the clearance capacity of SOD and other ROS scavengers, superoxide initiates a number of pathologic processes. This review examines pathologies involving superoxide, including: cancer, neurodegenerative diseases, ischemia/reperfusion injury, and inflammation. We will also explore the basic science principles of superoxide and SOD, including: SOD evolution, SOD mutations, biochemistry, physiology, and pathophysiology. In reviewing the basic science, clinical pathology, and therapeutic research, we hope to clearly demonstrate plausible pharmacologic targets of action. We have revised data about basic science, clinical pathology and therapeutic research in an effort to propose plausible pharmacological targets of action. The understanding of these aspects is critical in the accomplishment of a successful clinical intervention.