This review provides recent developments in the current status and latest synthetic methodologies of biphenyl derivatives. Furthermore, this review investigates detailed discussions of several metalated chemical reactions related to biphenyl scaffolds such as Wurtz–Fittig, Ullmann, Bennett–Turner, Negishi, Kumada, Stille, Suzuki–Miyaura, Friedel–Crafts, cyanation, amination, and various electrophilic substitution reactions supported by their mechanistic pathways. Furthermore, the preconditions required for the existence of axial chirality in biaryl compounds are discussed. Furthermore, atropisomerism as a type of axial chirality in biphenyl molecules is discussed. Additionally, this review covers a wide range of biological and medicinal applications of the synthesized compounds involving patented approaches in the last decade corresponding to investigating the crucial role of the biphenyl structures in APIs.