Abstract: Pyruvate dehydrogenase kinases (PDKs 1-4) can regulate the activity of the mitochondrial pyruvate dehydrogenase complex (PDC) to catalyse the oxidative decarboxylation of pyruvate, and then links glycolysis to the tricarboxylic acid cycle and ATP production. In this review, we summarize recent significant advances in our knowledge of the mechanisms regulating PDKs and the function of PDKs inhibitors in lowering blood glucose, decreasing damage during heart ischemia and also triggering apoptosis in cancer cells. PDKs will be a possible pharmacological targets in diabetes，heart ischemia and cancer therapy.

Key words: pyruvate dehydrogenase complex, pyruvate dehydrogenase kinases, diabetes, heart ischemia, cancer