​This review explores the advancements in drug delivery systems that incorporate bile salts since bilosomes that were developed over 20 years ago. Bile salts, recognized for their unique amphiphilic properties, have emerged as versatile agents in enhancing solubility, stability, and bioavailability of various therapeutics. We discuss the innovative formulations developed, including micelles, liposomes, and nanoparticles, that leverage bile salts to facilitate targeted and sustained release. The review also highlights the mechanisms by which bile salts improve drug absorption, particularly for hydrophobic compounds, and examines the evolving regulatory landscape surrounding these systems. Furthermore, we address challenges faced in clinical translation and future directions for research, emphasizing the potential of bile salt-based systems in personalized medicine. Our evaluation highlights the significant role of bile salts in advancing drug delivery technologies and their promise for improving therapeutic outcomes.​