A long held dogma in radiation biology has been that the effects of ionizing radiation arise only in the directly irradiated cells, and it was presumed that no effect would be expected in cells whose nuclei are spared from ionizing radiation. However, in the past twenty years, it has been suggested that irradiated cells are capable of production and secretion of signals to the neighboring unirradiated cells resulting in damage to these cells. This new challenging phenomenon is termed “the bystander effect”. Bystander effect can be reported in both cytoplasmic and nuclear irradiation in various cell types. Although the exact mechanisms of bystander effect production is not clearly defined yet, intercellular communication via gap junctions and lipid rafts, and secreted paracrine and endocrine soluble factors are potential suggested mechanisms. By this review article it has been aimed to summarize these mechanisms and the clinical reflections of bystander effect.