Chalcone is a privileged structure in medicinal chemistry, widely used as a scaffold for drug discovery due to its presence in many natural compounds and its ease of synthesis. This review highlights recent advances in chalcone research, covering its biosynthesis, synthetic methods, biological activities, and target identification. Chalcones are found in various natural sources, including plants, and have been extensively studied for their biological properties. They exhibit fluorescent properties, making them useful as chemical probes for mechanistic studies and imaging. The synthesis of chalcones involves various methods, including the Claisen–Schmidt condensation, cross-coupling reactions, and other strategies. These methods have been optimized for efficiency and yield, with some approaches using green chemistry principles. Chalcones have also been explored for their potential in detecting diseases and as fluorescent probes. The review also discusses their chemical reactivity, particularly their role as Michael acceptors in forming covalent bonds with thiols, which may contribute to their biological activities. Overall, chalcones represent a versatile and important class of compounds in medicinal chemistry.Chalcone is a privileged structure in medicinal chemistry, widely used as a scaffold for drug discovery due to its presence in many natural compounds and its ease of synthesis. This review highlights recent advances in chalcone research, covering its biosynthesis, synthetic methods, biological activities, and target identification. Chalcones are found in various natural sources, including plants, and have been extensively studied for their biological properties. They exhibit fluorescent properties, making them useful as chemical probes for mechanistic studies and imaging. The synthesis of chalcones involves various methods, including the Claisen–Schmidt condensation, cross-coupling reactions, and other strategies. These methods have been optimized for efficiency and yield, with some approaches using green chemistry principles. Chalcones have also been explored for their potential in detecting diseases and as fluorescent probes. The review also discusses their chemical reactivity, particularly their role as Michael acceptors in forming covalent bonds with thiols, which may contribute to their biological activities. Overall, chalcones represent a versatile and important class of compounds in medicinal chemistry.