Context matters - the complex interplay between resistome genotypes and resistance phenotypes

► The importance of distinguishing resistance phenotypes from resistome genotypes is discussed. ► Examples are provided of resistance genes acquired by pathogens which do not encode resistance in their native contexts. ► The role of environmental resistomes as the evolutionary reservoir of resistance is explained. ► Functional metagenomic selections are described as an ideal method for characterizing transferrable resistance genes. ► New evidence in support of recent exchange of resistance genes between human pathogens and environmental microbes is discussed.