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Dihydrochalcones are a class of secondary metabolites, whose demand in biological and pharmacological applications is rapidly growing. Phloretin is one of the best known and abundant dihydrochalcone characterized by the presence of 2,6-dihydroxyacetophenone pharmacophore. It is a versatile molecule with anticancer, antiosteoclastogenic, antifungal, antiviral, anti-inflammatory, antibacterial and estrogenic activities and able to increase the fluidity of biological membranes and penetration of administered drugs. In this review we have performed a critical evaluation of available literature as far as phloretin beneficial effects and activation/block of intracellular signal cascade are of concern. In addition, we supply useful information on its chemical properties, sources and bioavailability.