The development of perfluorocarbon (PFC) solutions as clinically useful oxygen-carrying agents has been a slow process because PFC is immiscible in aqueous solutions, including blood. Therefore, it has been necessary to develop emulsions for IV infusions. One such emulsion (fluosol) has been the most extensively studied and has been clinically tested. It has been shown that fluosol can transport oxygen in vivo when very high inspired oxygen concentrations are used and when high arterial oxygen tensions are achieved. Furthermore, it appears that the oxygen dissolved in PFC is very effectively delivered to and used by the tissues. In severely anemic patients, the PFC may deliver a very significant portion of the total consumed oxygen. It has been difficult to prove, however, whether fluosol has been clinically beneficial. It has a limited half-life (13 hours), the amounts infused have been quite limited, and the effect on patient outcome is unclear. Further, a number of adverse effects have been related to fluosol administration, most likely related to the emulsifying agent. PFC solutions thus remain experimental. Their greatest future use may be not as a blood substitute for treatment of anemia, but rather as an agent to improve microcirculatory oxygen delivery for treatment of ischemic tissues (ie, in stroke, myocardial infarction, burns, ischemic extremities). Further development of PFC emulsions is ongoing.