Exosomes are small membrane-bound vesicles released from cells. They incorporate proteins, nucleic acids, lipids, and metabolites to mediate intercellular communication and host-pathogen interaction. Exposure of ionizing radiation modifies cellular secretion and composition of exosomes. Exosomes contribute to radiation-induced bystander effect by decreasing cell proliferation, increasing DNA damage, and inhibiting DNA repair mechanism in bystander cells. On the contrary, evidences also suggest that exosomes derived from irradiated cells are involved in radioresistance in bystander cells. Additionally, exosome secretion from irradiated cells is involved in cancer progression and immunomodulation. This review summarizes our understanding of ionizing radiation-induced regulation of exosome function and raises the significance of possible application of exosome in radiotherapy.