Succinate dehydrogenase (SDH) has long been recognized as a mitochondrial enzyme crucial in both the citric acid cycle and the electron transport chain (ETC). However, recent research has shed light on an additional role of its substrate, succinate, beyond mere metabolism, particularly in conditions like tumorigenesis. Consequently, SDH is now acknowledged as a tumor suppressor, while succinate is identified as an oncometabolite. This chapter delves into contemporary discoveries concerning changes in SDH function that led to succinate buildup. These alterations encompass SDH mutations, mRNA expression control, posttranslational modifications, and natural inhibitors of SDH. Moreover, the chapter scrutinizes succinate’s impact on cancer development, exploring how it induces changes in epigenetics and metabolism and influences the transition of epithelium to mesenchyme, cell migration, and promotes angiogenesis. This chapter will also emphasize the diagnostic potential of SDH as markers for cancers displaying modified SDH expression.