Evidence accumulated over the past two decades has indicated that exposure of cell populations to ionizing radiation results in significant biological effects occurring in both the irradiated and non-irradiated cells in the population. This phenomenon, termed the ‘bystander response’, has been shown to occur both in vitro and in vivo. Experiments have indicated that genetic alterations, changes in gene expression and lethality occur in bystander cells that neighbor directly irradiated cells. Furthermore, cells recipient of growth medium harvested from irradiated cultures exhibit responses similar to those of the irradiated cells. Several mechanisms involving secreted soluble factors, gap-junction intercellular communication and oxidative metabolism have been proposed to regulate the radiation-induced bystander effect. In this review, our current knowledge of this phenomenon and its potential impact both on the estimation of risks of exposure to low doses / low fluences of ionizing radiation and on radiotherapy is discussed.