Silver (Ag) possesses a well-known antibacterial activity and has been used for medical treatment and cosmetics such as wound dressing and deodorant powders. Occupational Safety and Health Administration (OSHA) and Mine Safety and Health Administration (MSHA) proposed that the permissible exposure limit (PEL) for both metallic and most soluble Ag compounds should be 0.01 mg/m3. Argyria and argyrosis are known to be caused by deposition of insoluble Ag in the dermis and cornea/conjunctiva. However, the metabolic behavior and biological roles of Ag have not been well characterized in mammals. Ag can be absorbed into the systemic circulation from drinking water, and also through parenteral routes such as inhalation and dermal exposure. Experimental studies have demonstrated that Ag+ induces and binds to metallothionein I and II (MTs), which are cysteine-rich proteins, in cells. MTs are major cytoplasmic metal binding proteins and thereby reduce cellular damage caused by toxic heavy metals including Ag. Profiles of Ag distribution in MTs and other Ag-binding proteins can be determined using high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). This technique directly provides information on the intracellular behavior of Ag, which is important for elucidating the mechanism underlying Ag toxicity. Silver nanoparticles (AgNPs) are also commercially used mainly as antimicrobial agents. Despite the widespread use of AgNPs, relatively few studies have been undertaken to evaluate the health effects of AgNP exposure. In the present paper, we discuss the absorption, toxicodynamics, and metabolism of both Ag and AgNPs in mammals and their health effects.