Blood transfusion is a remarkably safe, routine clinical procedure. However, the need for sophisticated blood processing, storage and cross-matching, coupled with increasing concerns about the safety of blood products, has fuelled the search for safe and efficacious substitutes. Candidate materials based on modified haemoglobin (including recombinant molecules) or highly inert, respiratory gas-dissolving perfluorinated liquids (perfluorochemicals) have been developed. The latter are immiscible in aqueous systems and must, therefore, be injected as emulsions. Second-generation perfluorochemical emulsions are available and in clinical trials as temporary intravascular oxygen carriers during surgery, thereby reducing patient exposure to donor blood. One commercial product is currently under Phase III clinical evaluation, with regulatory approval expected within 1 2 years. Other biomedical applications for perfluorochemicals and their emulsions include their use as pump-priming fluids for cardiopulmonary bypass, lung ventilation fluids, anti-cancer agents, organ perfusates and cell culture media supplements, diagnostic imaging agents and ophthalmologic tools. Novel applications for perfluorochemicals as immunomodulating agents are also being explored.