Bacterial persisters are phenotypic variants that form under stress, cause recurrent infections and also possess antibiotic tolerance. The use of colloidal silver to combat persisters seems to be a promising alternative since bacterial tolerance towards metals or metal ions has not been reported. The objective of this study was to determine the effect of colloidal silver on E. coli K-12 NCIM 2665 persisters to Ampicillin. The study determined the effect of colloidal silver on E. coli persisters to Ampicillin. The combined action of Ampicillin and silver against persisters was determined by checkerboard assay. Tolerance of log phase population of E. coli K-12 NCIM 2665 to silver and whether persisters to silver are formed was also determined. The Fractional Inhibitory Concentration (Sigma FIC) index for Ampicillin and colloidal silver was determined to be <= 1 which indicates an additive effect. A five-log reduction in log phase population and two log reduction in antibiotic persisters was observed after one hour exposure to 16ppm silver; indicating the effectiveness of colloidal silver. Colloidal silver decreases the formation of Ampicillin persisters as well as prevents the survival of existing Ampicillin persisters. In order to combat recurrent bacterial infections, methods need to be found to reduce the formation of pathogenic bacterial persisters or to enhance the susceptibility of persisters to antibiotics. The results of the present study imply that colloidal silver can be used as an anti-persister strategy directly or in combination with an antibiotic.