Drosophila melanogaster is a highly attractive model system for the study of numerous biological questions pertaining to development, genetics, cell biology, neuroscience and disease. Until recently, our ability to manipulate flies genetically relied heavily on the transposon-mediated integration of DNA into fly embryos. However, in recent years significant improvements have been made to the transgenic techniques available in this organism, particularly with respect to integrating DNA at specific sites in the genome. These new approaches will greatly facilitate the structure-function analyses of Drosophila genes, will enhance the ease and speed with which flies can be manipulated, and should advance our understanding of biological processes during normal development and disease.