Biologists have strived to understand the origins of morphological and behavioral differences between individuals since long before Darwin’s 1859 “Abstract” to his Big Book. While Darwin’s work made it abundantly clear that huge amounts of variation exist within and between species, the mechanism by which this variation was produced and passed on from generation to generation was not clear. We now know that DNA is the hereditary material. Furthermore, the complete DNA sequences from an immense range of organisms has revealed an enormous amount of DNA variation that could cause the morphological and behavioral differences Darwin highlighted in his books. Which of this genetic variation causes phenotypic variation? And what roles do natural or sexual selection play in its evolution? This thesis explores the role that evolutionarily new genes, the functional units of DNA, play in shaping the evolution of fitness and the genome through an investigation of genes found in a single species of fruit fly. I use precise genetic manipulation to show that at least 27% of Drosophila melanogaster-specific genes, while young, have essential roles in fly development and reproduction. Furthermore, I use empirical population genetics analyses to show that species-specific genes are frequently strongly selected, and, combined with my functional data, suggest that new genes are likely primarily selected for their male-beneficial functions. Altogether, this work shows that the genes underlying important processes such as development and reproduction can rapidly change and that this process is strongly influenced by selection. Supplementary File 1 contains tandem duplication calls in the DPGP2 produced in Chapter 4 and is available online.