The number of genes known to cause human monogenic diseases is increasing rapidly. For the extremely large, genetically and phenotypically heterogeneous group of intellectual disability (ID) disorders, more than 600 causative genes have been identified to date. However, knowledge about the molecular mechanisms and networks disrupted by these genetic aberrations is lagging behind. The fruit fly Drosophila has emerged as a powerful model organism to close this knowledge gap. This review summarizes recent achievements that have been made in this model and envisions its future contribution to our understanding of ID genetics and neuropathology. The available resources and efficiency of Drosophila place it in a position to tackle the main challenges in the field: mapping functional modules of ID genes to provide conceptually novel insights into the genetic control of cognition, tailored functional studies to improve 'next-generation' diagnostics, and identification of reversible ID phenotypes and medication. Drosophila's behavioral repertoire and powerful genetics also open up perspectives for modeling genetically complex forms of ID and neuropsychiatric disorders, which overlap in their genetic etiologies. In conclusion, Drosophila provides many opportunities to advance future medical genomics of early onset cognitive disorders.