Several reports have revealed the superior biological activity of metal ion-flavonoid complexes when compared with the parent flavonoid. Among the different metal ions explored, vanadium and its compounds are in the forefront because of their anticancer and antidiabetic properties. However, the toxicity of vanadium-based ions and their inorganic derivatives limits their therapeutic applications. Complexation of vanadium with flavonoids not only reduces its adverse effects but also augments its biological activity. This Review discusses the nature of coordination in vanadium-flavonoid complexes, their structure-activity correlations, with special emphasis on their therapeutic activities. Several investigations suggest that the superior biological activity of vanadium complexes arise because of their ability to regulate metabolic pathways distinct from those acted upon by vanadium alone. These studies serve to decipher the underlying molecular mechanism of vanadium-flavonoid complexes that can be explored further for generating a series of novel compounds with improved pharmacological and therapeutic performance.