Clinical relevance of sodium/glucose cotransporter 2 (SGLT2) inhibitors has been rapidly evolving across several therapy areas, apart from type 2 diabetes mellitus. While some of these developments are based on recognized scientific explanations, unexpected study findings have also shaped much of our present understanding. As the role of these agents evolves in various facets of cardiology, nephrology, hepatology and endocrinology, their optimum clinical value propositions should be realized in line with the principles of personalized medicine. An updated pharmaco-ergonomic qualification tool, based on the present evidence with these agents, would be a step in this direction. This review describes the present evidence on diverse pharmacological and therapeutic aspects for various SGLT2 inhibitors, as an attempt to provide useful guidance for optimum application in clinical practice.