he fruit fly Drosophila melanogaster has arguably been the single most influential model laboratory organism that has allowed us to understand the genetic basis for the major events of embryonic development in animals. Axial patterning, embryonic versus extra-embryonic specification, body regionalization, and establishment of the three layers and the germ line have all been elucidated in exquisite molecular detail in the fruit fly, and many of the genes controlling these processes are conserved across animals. However, these processes operate very differently in fruit flies than in most insects and other arthropods. Moreover, it is clear that while individual genes can be highly conserved across organisms, they can operate in different ways to generate distinct molecular mechanisms to achieve the same goals in different animals. Our lab has therefore investigated the genetic control of development using a number of different “alternative” laboratory model organisms. Comparing the results with D. melanogaster suggests that in many cases, the fruit fly mechanisms are highly derived, having diverged from an ancestral state that was very different, and that is commonly observed in most other arthropods. Here we use the process of germ cell specification as a case study to illustrate how studying other insects can yield insights into ancestral animal mechanisms for establishing the germ line. Finally, we discuss ongoing efforts to develop quantitative imaging analysis methods for such organisms. We aim to apply these methods to understand the evolution of mechanisms that control the movements and organization of early embryonic cells during establishment of the major body axes and tissue types.