The increasing challenge of antibiotic resistance requires not only the discovery of new antibiotics, but also the development of new alternative approaches. Herein, the synergistic antibacterial activity of silver nanoparticles and hydrogen peroxide combination is reported. Unlike the bacteriostatic or slightly bactericidal activity achieved by using each agent alone, using these two agents in combination, even at relatively low concentrations, resulted in complete eradication of both the Gram negative Escherichia coli and the Gram positive Staphylococcus aureus in short treatment times indicating a clear synergistic effect between them. Modifying the surface chemistry of silver nanoparticles and the accompanied change in their surface charge enabled a further enhancement of such synergistic effect implying the importance of this aspect. Mechanistically, a Fenton-like reaction between silver nanoparticles and hydrogen peroxide is discussed and hypothesized to be the basis of the observed synergy. Achieving such a significant antibacterial activity at low concentrations reduces the potential toxicity of these agents and hence enables their utilization as an alternative antibacterial approach in wider range of applications.