Superoxide and its derived ROS (reactive oxygen species) have been considered for a long time to be generated as toxic by-products of metabolic events. Although ROS generated in low amounts are able to act as signalling molecules, ROS appear to also play a major role in aging and in the pathogenesis of diseases such as inflammation, diabetes and cancer. Since superoxide formation, in particular in mitochondria, is often considered to be an initial step in the pathogenesis of these diseases, improper function of the MnSOD (mitochondrial superoxide dismutase; SOD2) may be critical for tissue homoeostasis. However, the underlying regulatory mechanisms appear to be multiple and this article summarizes current aspects by which MnSOD can regulate carcinogenesis under various conditions.