Since the founding of Drosophila genetics by Thomas Hunt Morgan and his colleagues over 100 years ago, the experimental induction of mosaicism has featured prominently in its recognition as an unsurpassed genetic model organism. The use of genetic mosaics has facilitated the discovery of a wide variety of developmental processes, identified specific cell lineages, allowed the study of recessive embryonic lethal mutations, and demonstrated the existence of cell competition. Here, we discuss how genetic mosaicism in Drosophila became an invaluable research tool that revolutionized developmental biology. We describe the prevailing methods used to produce mosaic animals, and highlight advantages and disadvantages of each genetic system. We cover methods ranging from simple "twin-spot" analysis to more sophisticated systems of multicolor labeling.