AimsRecent advances in mass spectrometry have demonstrated that higher plants discriminate stable Zn isotopes during uptake and translocation depending on environmental conditions and physiological status of the plant. Stable Zn isotopes have emerged as a promising tool to characterize the plants response to inadequate Zn supply. The aim of this review is to build a comprehensive model linking Zn homeostasis and Zn isotopic fractionation in plants and advance our current view of Zn homeostasis and interaction with other micronutrients.