Bystander and low-dose-rate effects influence the dose-response relationship in a manner not predicted by current dosimetric methodologies. Radiation-induced bystander effects refer to biologic responses in cells that are not traversed by an ionizing radiation track and, thus, not subject to direct energy deposition; that is, the responses occur in nonirradiated cells. Low-dose-rate hypersensitivity effects have been documented as a reduction in the survival of cells irradiated at dose rates of 0.1-1.0 Gy/h, with total doses ranging from 1.5 to 5 Gy. For humans undergoing external radiotherapy, evidence of bystander events has been observed in the form of abscopal effects, wherein irradiation of one portion of the anatomy affects a portion outside the radiation field, whereas low-dose-rate hypersensitivity has not been described. In this report, the historical literature is briefly reviewed, key experiments are summarized, and current understanding of the factors thought to be involved in the bystander and low-dose-rate effects is conveyed. The mechanisms associated with these events are still being investigated, and questions remain on their impact in radionuclide therapy. Although current findings do not yet sufficiently justify changing traditional dose estimates used to predict the outcomes of radionuclide therapy, it is important to appreciate the potential importance of these effects and to begin revising methods to reflect the emerging empiric and mechanistic knowledge.