Crop nutrition can be manipulated through agronomy and genetics, to optimize the delivery of essential mineral nutrients to humans and livestock. Our focus is on magnesium, which is an essential element in plant biology but also the fourth most common cation in the human body. Hypomagnesaemia is recognized as a global clinical problem. Our primary interest is to identify genes involved in Mg homeostasis in the model species Arabidopsis thaliana, a domain that is relatively unexplored. To achieve this goal, our experimental outlines are to use natural changes in Mg tissue concentrations and to identify transcriptome changes associated with Mg depletion and restoration. (i) The first approach exploits the variation of Mg concentration in Arabidopsis mutants and natural accessions as a source of diversity. We observed a 50% difference variation in the tissue Mg concentration between the most contrasted accessions. (ii) Because the knowledge about the impact of Mg deficiency on physiological processes was scarce, we proceeded to transcriptome analyses to provide non-biased hints about targets of Mg starvation. Early observations were the alteration of rhythmic expression of circadian clock component genes in roots, the triggering of the abscisic acid signalling. Later, higher expression was observed of genes in the ethylene biosynthetic pathway, in the reactive oxygen species detoxification and in the photoprotection of the photosynthetic apparatus. Unlike other mineral deficiencies, putative Mg transporters genes were not induced (post-transcriptional induction cannot be excluded).