Naturally and synthetically derived hybrid molecules are an attractive source for therapeutic agent development due to their dual or multiple modes of action and other advantages. Coumarin and chalcone, two important classes of natural products affording diverse pharmacological activities, make themselves ideal blocks for building a coumarin–chalcone hybrid scaffold as a bioactive agent. Provoked by the promising medicinal application of such hybrids, the scientific community has reported dozens of coumarin–chalcone hybrids with a wide spectrum of biological properties including anticancer, antimicrobial, antimalarial, antioxidant, antitubercular and so on, through synthetic hybridization strategy or characterization from natural sources. The present mini review provides a systematic summary on natural and synthetic agents of coumarin–chalcone hybrids on the basis of their therapeutic properties. It is expected to assist medicinal chemists in the effective and successful development of coumarin–chalcone hybrids.