Flavonoids are among the most ubiquitous phenolic compounds found in nature. These compounds have diverse physiological and pharmacological activities such as estrogenic, antitumor, antimicrobial, antiallergic, and anti-inflammatory effects. They are well-known antioxidants and metal ion-chelators. In the present review, biotransformations of numerous flavonoids catalyzed mainly by microbes and few plant enzymes are described in four different flavonoid classes, viz., chalcones, isoflavones, catechins, and flavones. Both phase I (oxidative) and phase II (conjugative) biotransformations representing a variety of reactions including condensation, cyclization, hydroxylation, dehydroxylation, alkylation, O-dealkylation, halogenation, dehydrogenation, double-bond reduction, carbonyl reduction, glycosylation, sulfation, dimerization, or different types of ring degradations are elaborated here. In some cases, the observed microbial transformations mimic mammalian and/or plant metabolism. This review recognizes Norman Farnsworth, who through his fascination and hard work in pharmacognosy has fostered the excitement of discovery by numerous students and faculty far and beyond the halls of the University of Illinois at Chicago. It is with grateful thanks for these efforts that we dedicate this review to him.