Copper and iron are essential minerals for plant growth, and human health and nutrition. Cadmium, on the other hand, is a highly toxic element that competes with essential elements for uptake and partitioning, and poses a threat to crop productivity and human health. While substantial progress has been made towards understanding how plants maintain homeostasis of copper and iron, how it is achieved in an environment that also contains cadmium is still poorly understood. Two separate studies have identified cross-talk between cadmium toxicity and copper and iron homeostasis in Arabidopsis thaliana. With respect to the effect of cadmium on copper homeostasis, we show that cadmium mimics transcriptional copper deficiency responses that result in increased copper uptake and likely intracellular copper reallocation in A. thaliana. These effects of cadmium are attributed to a transcription factor, SPL7, and its downstream targets, copper transporters COPT1, COPT2, and COPT6; and Cu/Zn superoxide dismutases, CSD1 and CSD2. With respect to the effect of cadmium on iron homeostasis, we found that cadmium increased expression of an oligopeptide transporter, OPT3. Studies of the biological relevance of this phenomenon revealed that OPT3 is a phloem-specific iron transporter that loads iron into the phloem, controls iron redistribution from mature to developing tissues and seeds, and is involved in systemic iron signaling. We also found that OPT3-dependent systemic iron signaling is important for controlling cadmium partitioning: loss of OPT3 function leads to increased accumulation of cadmium while decreasing accumulation of iron in seeds of A. thaliana. Together, these data suggest that manipulation of the components of essential mineral element homeostasis provide promising avenues for targeted biofortification strategies directed at increasing mineral nutrient density while preventing the entry of toxic elements such as cadmium into edible portions of crops.