Persistent DNA damage leads to genomic instability, a driver of various illnesses. This points to the importance of the detection of DNA damage. In the last few decades, Drosophila melanogaster has emerged as a powerful alternative model system to animal experimentation in toxicological research, including genotoxicity studies. Several genetic and molecular methods have been developed to detect DNA damage in the model system. This chapter reviews the different approaches to detecting and quantifying DNA damage using D. melanogaster and the utility of D. melanogaster for assessing genotoxicity.