The Diptera, with nearly 150,000 described species, are not only taxonomically diverse, but numerically abundant and of extreme trophic, medical and veterinary significance. Consequently, knowledge about the origin and relationships of these insects is of considerable importance. Although one of the best-supported monophyletic orders of Insecta, relationships within the Diptera remain uncertain. The challenge of generating a robust phylogeny of Diptera has attracted the attention of many leading systematists (e.g., Willi Hennig) during the past four decades. Our laboratory has been one of the major participants in this research, especially in the generation of morphologically based hypotheses on the relationships of lower Diptera. This work has provided a framework for many additional morphological and molecular studies, and contributed significantly to an ongoing National Science Foundation Assembling the Tree of Life project. Through the latter, morphological and molecular data sets are being analyzed by our lab and collaborators throughout the world, including specialists from the U.S., Canada, Australia, Europe, Asia, and South America.