Archaea occupy a considerable diversity of niches ranging from extreme of pH, salinity to temperature that cannot be tolerated by other forms of life. There is an increasing consciousness that they have a key role both on the biogeochemical cycling of elements and in the bioremediation of polluted habitat. A greater understanding of metal homeostasis and resistance to toxic compounds in this life domain is required to design new strategies for the bioremediation of contaminated sites. This review describes the strategies developed by Archaea to transform xenobiotic compounds and metal ions present in the environment. The adaptation and/or response to such chemicals and the molecular mechanisms of resistance evolved in Archaea are discussed.