H2AX is a histone variant that is systematically found and ubiquitously distribute throughout the genome. DNA double strand breaks induce γ-H2AX foci which became the gold standard for detection of double strand break. Many drugs and environmental factors can damage DNA, so understanding and predicting the outcomes of exposure to DNA-damaging agents is an important challenge in drug development and in environmental health research. Measurements of γ-H2AX phosphorylation are currently the most sensitive way to detect IR-induced DNA damage and to measure the extent of DSB repair. Measurements of γ-H2AX foci could therefore be a possible approach to monitor DSBs or DSB repair in cancer patients during treatment with radiotherapy or chemotherapy as a way to personalize the dosing. It is also possible that γ-H2AX measurements could be used for radiation biodosimetry for nuclear plant workers or in the general public after nuclear accidents as well as exposure to potentially DNA damaging environmental toxins. Many techniques are there to detect and to measure γ-H2AX foci, these and other as yet unresolved questions are discussed and tried to find out the solution.