Flies in the genus Drosophila have been the dominant model organisms in genetics for over a century and, with a dozen complete sequences now available, continue as such in modern comparative genomics. Surprisingly, estimates of genome size for this genus have been relatively sparse, covering less than 2% of species. Here, best practice flow cytometric genome size estimates are reported for both male and female flies from 67 species from six genera in the family Drosophilidae, including 55 species from the genus Drosophila. Direct and phylogenetically corrected correlation analyses indicate that genome size is positively correlated with temperature-controlled duration of development in Drosophila, and there is indication that genome size may be positively related to body size and sperm length in this genus. These findings may provide some explanation for the streamlined genomes found in these insects, and complement recent work demonstrating possible selective constraints on further deletion of noncoding DNA.