Flavonoids are a class of natural polyphenolic compounds sharing a common 2-phenyl-3,4-dihydro-2H-1-benzopyran (flavan) backbone. Typically known for their antioxidant activity, flavonoids are also being investigated regarding antitumour and antimicrobial properties. In this review, we report on the complexation of both natural and synthetic flavonoids with ruthenium as a strategy to modulate the biological activity. The ruthenoflavonoid complexes are divided into three subclasses, according to their most prominent bioactivity: antitumour, antimicrobial, and protection of the cardiovascular system. Whenever possible the activity of the ruthenoflavonoids is compared with that of commercial drugs for a critical assessment of the feasibility of using them in future clinical applications.