Non-targeted effects, i.e., those responses in cells or tissues that were not subject to energy deposition events after localized exposure to ionizing radiation, are well established. While they are not a universal phenotype, when they do occur they can be associated with subsequent tissue or whole body responses. Here it is argued that non-targeted effects are a tissue level response to restore equilibrium within an organ system, and thus restore tissue homeostasis. This “adaptive homeostasis” has evolved in response to a variety of environmental and other such stresses an individual is exposed to in their lifetime. These non-targeted effects are not likely to impact significantly on estimates of potential risks associated with radiation exposure because they are presumably “built into” current risk estimates. However, they could have implications for radiation carcinogenesis, by driving processes in targeted and non-targeted cells that could eliminate transformed cells or transform cells from a normal phenotype to a phenotype associated with malignancy within a tissue.