Drosophila (fruitfly) and Caenorhabditis (nematode worm) are useful model organisms for understanding many molecular and cellular mechanisms of human disease. Work on them is powered by versatile gene discovery methods, output of their genome projects, and a biology that has much in common with that of humans. They contain homologues of most human disease genes. Many aspects of human disease, and of defences against disease, are also found in flies and worms. These include cancer, ageing, neurodegeneration, infectious disease, innate immunity, and dysfunction of neurotransmitter and endocrine systems.