Silver uptake and metabolism is linked to that of copper. Ag(I) is taken up via the copper transporter 1 (CTR1), binds to copper chaperones and is trafficked to the trans-Golgi network (TGN), where it is imported via a Cu-ATPase. The Ag(I)-laden TGN vesicles travel to the membrane and Ag(I) is exported from the cell. Ag(I) has been shown to replace Cu(I) in a number of cuproenzymes. Unlike Cu(I), Ag(I) is not involved in Fenton–Haber–Weiss chemistry, yet it can be reduced to Ag(0), a reaction that would use up cellular reducing capacity. In addition, silver can interfere with mitochondrial function resulting in reactive oxygen species (ROS) production and oxidative damage, and it also affects membrane integrity and DNA synthesis. Ag is exceptionally toxic to bacteria and aquatic organisms, but is generally thought to be relatively benign to humans. This property has seen a rise in the use of Ag as an antimicrobial agent, and in recent years the production and use of Ag-nanoparticles (Ag-NPs) has expanded rapidly. Ag-NPs are known to cause cytotoxicity and accumulate in tissues, but it is uncertain whether humans or wildlife are exposed to concentrations that are sufficient to pose a health risk. The chapter will discuss the cellular transport process, intracellular handling and toxicity of Ag(I) and Ag-NP and mechanisms of bacterial Ag resistance.