Abstract Quinoline derivatives are a heterocyclic family of structurally diverse and pharmacologically relevant compounds of interest in medicinal chemistry. The molecules exhibit a wide range of biological functions, such as antimicrobial, anti‐inflammatory, anticancer, antimalarial, antioxidant and antibacterial agents, which enable them to be considered useful as drug discovery and development scaffolds. This review aims to give a general overview of pharmacological potential of quinoline derivatives including their action mechanisms, clinical and therapeutic use. Further, the recent reports on solubility optimization, approach to drug delivery, and formulation are addressed with the strong interest in their role in enhancing pharmacokinetic characteristics and clinical translation. Special emphasis is placed on the up‐to‐date studies on synthetic strategies and hybrid molecules that support the flexibility of the quinoline skeleton in terms of its structure. Through a combination of mechanistic understanding and therapy, this review provides an overview of the advancements made in quinolines research and prospects of developing next generation analogs of quinolines with superior efficacy and safety.