The criteria for the selection of perfluorochemicals destined to serve as oxygen carriers in second‐generation blood substitutes are critically discussed in light of the presently available body of data. The need for pure, well‐defined, reproducible, industrially feasible perfluorochemicals, in order to attain the degree of reliability desirable for their use in medicine, is stressed. Particular attention is given to the inverse excretion rate versus emulsion stability relationship and to its sharp dependence on molecular weight. The range of acceptable molecular weights is established as 460–520. Oxygen‐dissolving capacity, rheologic characteristics, and intravascular persistence are also discussed. The need for standard methodology and experimental protocols is reaffirmed. Perspectives are evaluated, in particular, with the aim of easing certain of the present limitations.