Exposure to hydrogen fluoride, whether in its gaseous or liquid form, can cause severe metabolic disturbances and even death. We present a case of an adult gentleman who was successfully treated after exposure to a large vapor cloud of hydrogen fluoride while working at a refinery. The patient exhibited various symptoms and signs including dermal, ophthalmic, and pulmonary irritation. He was successfully treated using various forms and routes of calcium gluconate administration. The prompt reaction and attention of the patient and his co-workers to this life-threatening exposure, and the recognition and awareness of the emergency department personnel limited the systemic absorption and toxicity. A comprehensive review of the literature is presented.