Accurately assessing the genotoxic potential of foreign agents (for example, chemicals, nanoparticles, or nanoplastics) and gene editing methods is absolutely critical in protecting human health by limiting our exposure to harmful genotoxicants that may cause cancer and developmental defects through DNA damage. In the dichotomy of benefit vs. risk, on the other hand, the potential benefit may far outweigh the risk of exposure. Ionizing radiation, for example, is a direct-acting physical genotoxin, but the benefits of its use in diagnosis are unequivocal. The question is not, therefore, “Is the article genotoxic?” The question is, “How genotoxic?” Of course, this is dependent on dose, but it is also dependent upon the biology of the cell that determines the response to the genotoxic insult. It is, therefore, critical that the methods we use within the field of genotoxicology can identify genotoxic hazards accurately, and are also able to contextualize the findings in terms of biological relevance. This Methods Collection will include the traditional endpoints of genotoxicity, but will also include technologically advanced methods that have higher throughput and greater sensitivity, that incorporate novel biomarkers, and that are centered on whole-omics approaches. The collection will also support the reproducibility of these experiments, which is particularly pertinent in the field of genetic toxicology.