Recent developments in Mn biology have added new physiological and pathophysiological roles of this essential metal ion to the already existing repertoire of indispensable biological roles of Mn ions. Notably, the discovery of Mn2+ specific transporters, maladies related to mutations in these transporters, and evidence of the role of labile Mn2+ species as anti-oxidants have initiated studies targeted at elucidating Mn ion regulation and pathways implicated in pathological conditions. Closely inter-linked with the quest for understanding metal ion homeostasis are basic questions like “How are metal ions installed in their correct biological addresses where they need to function?” and “Are dynamic changes in metal ion distribution functionally relevant?” These questions become more critical in the context of Mn2+ ions, which have inherently low binding affinities toward most ligands and hence would always face competing metal ions in the biological milieu. In the emerging context of functional roles of the labile Mn2+ ion pool, the development of chemical tools and techniques that can provide information on the location, distribution and dynamic changes in these parameters under physiological and pathophysiological conditions becomes imperative. In this frontier article, we discuss the challenges that had left Mn2+ ions lagging behind in the race for the development of chemical tools and recent approaches that addressed these challenges to develop tools and techniques that can illuminate Mn ions in living systems.< Réduire