Increasingly, monovalent silver cations are being considered as an alternative biocide in water distribution systems. The objective of this study was to understand how bacteria respond when challenged with silver. The approach used included cultivation of Escherichia coli in planktonic and sessile phases, exposing biomass to a solution of silver nitrate and evaluating genetic responses using commercial Affymetrix microarrays. Experimental results showed that lower pH enhanced silver toxicity in a dose-dependent manner. Sessile biomass demonstrated resistance to silver, and the microarray results indicated that the genetic mechanism for silver resistance was similar to the mechanism for copper resistance including upregulation of efflux pumps as well as upregulation of metal oxidoreductases. The gene, copA, a P-type ATPase efflux flux, was upregulated in response to silver exposure, and the gene of CusCFBA, a Cu(I) efflux pump, was also upregulated. The gene of CueO, a robust cuprous oxidase, was also upregulated and may have reduced silver toxicity through oxidation of silver ions. This study is significant because it provides baseline data to understand the genetic response of bacteria to silver biocides.