Diphoterine (Laboratoire Prevor, Valmondois, France) is an active, amphoteric, polyvalent, chelating, slightly hypertonic decontamination solution for chemical splashes to the skin and eyes. It chemically binds a large number of chemical substances present on the skin surface without causing a significant release of heat (exothermic reactions). Because of its amphoteric properties, it can bind chemically opposite substances such as acids and bases or oxidizers and reducing agents. No adverse effects have been observed in an ongoing postmarketing surveillance program during many years of use in European industrial facilities. Diphoterine has more recently been used in hospitals for delayed management of chemical burns to the skin and eyes. There is interest in having protocols for both immediate and delayed diphoterine use for skin decontamination. Whereas studies of diphoterine efficacy, clinical and in vitro or ex vivo, have been published or are in the process of being prepared for publication, no review has yet been published focusing solely on the safety of this decontamination solution. Therefore, all available studies on the safety of diphoterine are described here, including recent studies demonstrating no harmful effects on the skin. Diphoterine can be used, even on damaged skin, without toxic, irritant, allergenic, or sensitizing effects.