Certain plants (so-called metallophytes) have adapted to otherwise toxic metal concentrations and thrive on metal contaminated soil. Some of these species not only show exceptional tolerance but even hyperaccumulate metals/metalloids such as Ni, Zn, Cd or As in their shoots to quantities sometimes exceeding 1 % of their dry weight. Considerable interest in plant metal hyperaccumulation has been evoked by the concept of phytoremediation, i.e. the use of plants for the cleaning up of metal-contaminated soil and water. Molecular understanding of plant metal accumulation determinants has numerous additional biotechnological implications. Health-threatening human deficiencies in trace metals appear to be widespread in developing countries and possibly worldwide. Enhancing Zn accumulation in edible parts might help in enriching diets for Zn. Conversely, most of the toxic non-essential elements such as Cd enter the human body via plant-derived material.We have adopted a comparative genomics approach to elucidate the molecular mechanisms underlying metal hyperaccumulation. We are studying the hyperaccumulator Arabidopsis halleri, which grows at sites in the Harz mountains and other mining areas, and its relative, the model plant A. thaliana. DNA array-based transcriptome studies revealed a “hyperaccumulation syndrome” and suggest mechanisms explaining the evolution of this particular adaptation to an extreme environment.