Nitroglycerin (NTG) (glyceryl trinitrate) was synthesized by the Italian chemist Ascanio Sobrero in Paris in 1846. A very unstable explosive, Alfred Nobel while working on explosives, combined it with Kiselguhr and patented it as dynamite in 1867. NTG was introduced in 1879 in medicine in the treatment of angina pectoris by the English doctor William Murrell. NTG-induced headache was quickly recognized as an important adverse event both in the industrial use of NTG, where it was used to produce dynamite, as well as in the use of NTG as drug. This review traces the evolution of our understanding of NTG headache.