Multivesicular endosomes contain membrane vesicles which can be released into the extracellular environment as exosomes. This review describes the role of exosome secretion in the remodeling of the red cell plasma membrane during the last stage of erythropoietic differentiation. Herein, we propose that the exosome biogenesis involves several mechanisms of protein sorting and leads to partial or complete loss of membrane activities, in some cases in a regulated way.