It is now apparent that the target for the biological effects of ionizing radiation (IR) is not solely the irradiated cell(s), but also includes the surrounding cells/tissue as well. Radiation-induced bystander effects (BSEs) are defined by the presence of the biological effects of radiation in cells that were not themselves in the field of irradiation. Decreased plating efficiency, increased sister chromatid exchanges, oncogenic transformation, among other endpoints have been used to describe the BSE. Two primary means have been established for the transmission of the bystander signal; one is mediated by gap-junction intracellular communication, and the other is initiated through the secretion of factors from irradiated cells. While the basis for these phenomena have been established in cell culture systems, there is also evidence for their presence in vivo. This in vivo effect may contribute to increased tumor cell killing, and may also play a role in the abscopal effects of radiation, where radiation responses are seen in areas separated from the irradiated tissue. Although the precise molecular components and mechanisms remain unknown, their discovery will shed new light on the role of the BSEs in radiation risk assessment, and clinical radiotherapy in the clinic.