The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor with several structural types, performing a myriad of molecular mechanisms. The RAGE-ligand interactions play important roles in maintaining latent chronic inflammation, and oxidative damage underlying various pathological conditions like metabolic syndrome (MetS), neurodegenerative diseases, stroke, cardiovascular disorders, pulmonary disorders, cancer and infections. RAGE is thoroughly explored in knockout animals and human trials, targeted by small molecule inhibitors, peptides, diet, and natural compounds. But it is yet to be incorporated in the mainstream management of any ailment. This review performs an appraisal of the pathological mechanisms influenced by RAGE to uncover its prospects as a biomarker while also assessing its power to become a promising therapeutic target.