Reviewed here are recent attempts to produce protein-based artificial oxygen carriers ("blood substitutes"). Most of these involve chemical or physical modifications on hemoglobin, although a recent line of research using hemerythrin instead of hemoglobin is also described. The focus is set on the extent to which these modifications alter the redox reactivity of the proteins, and on ways in which this can be done systematically and purposefully, within the framework of a working hypothesis where redox side-reactions hold an important role in the physiological outcome of experimental transfusions with artificial oxygen carriers.