Inconceivable as it is, it has been proved that animals can survive after having had their blood massively or even totally replaced by emulsions of perfluorinated compounds in salines. “Bloodles” rats charged with an emulsion of perfluorotri‐n‐butylamine survived a five hour period in an atmosphere containing 50% oxygen and 50% carbon monoxide, i.e. in conditions where the transport of oxygen by the red cells is entirely blocked. This review discusses: (1) the experiments which have demonstrated the capability of blood substitutes based on perfluorinated compounds to sustain life; (2) the characteristics and preparation of the relevant perfluoro compounds and the production and handling of their emulsions; (3) their “physiology”, i.e. toxicity, life‐span in the blood‐stream, effect on the organs and their functions, and excretion properties. Obstacles remaining to be overcome in order to provide a safe blood substitute for medical practice include the availability of numerous series of well‐defined pure and inert perfluorinated chemicals, the production of stable emulsions, the optimization of fluid balance, and the attainment of reasonable excretion rates. The accent is placed upon the role of the chemist in the progress of this research.