Hydrofluoric acid (HF) induces severe skin necrosis through corrosive damage and tissue toxicity. As it is only partially dissociated (pKa 3.2), the small HF molecule penetrates deeply into tissues. When absorbed into the circulatory system, HF can dissociate into H+ and F- ions (the latter binds calcium and magnesium and releases potassium from erythrocytes), which together with resultant severe metabolic acidosis may result in cardiovascular system toxicity with dysrhythmias and death. A summary review of recent experimental data from human skin explant ex vivo studies was performed. Lesions due to 70% HF appeared withinthe first minute in human skin explants and full skin penetration was observed within 5 minutes. This experimental technique using human skin explants obtained from abdominoplasty patients preserved ex vivo offers a method for evaluating the effects of corrosive substances and their mitigation with active decontamination solutions versus water irrigation in intact human skin. Hexafluorine® used in this ex vivo model was more efficacious than tap water irrigation followed by calcium gluconate ointment. Decontamination of skin hydrofluoric acid exposure should be ideally started within the first minute. Traditionally, the initial decontamination has been with tap water in an industrial safety shower following recommendations such as those found in the ANSI/ISEA Z358.1-2009 Standard or similar European Norms, which has mitigated the effects of HF skin exposure in certain cases. However, ex vivo human skin explants data suggest that, when available, Hexafluorine ® may be a more efficacious alternative decontamination solution. In every case, calcium gluconate should be administered if it is required by medical protocol or if a burn has already appeared.