All forms of life on Earth share a common ancestry. As a consequence, Homo sapiens shares a large number of genes essential for the development and maintenance of multicellular life with "simple" animals, such as the fruit fly Drosophila melanogaster and the nematode worm Caenorhabdites elegans. Indeed, Drosophila and C. elegans have successfully been used to unravel fundamental mechanisms underlying animal development. The sequencing of their genomes has revealed that a surprisingly large proportion of genes relevant for human disease have counterparts in the worm and in the fly. This includes many oncogenes and tumour suppressor genes and provides us with a unique opportunity to exploit the advantages of simple model organisms to further our understanding of the molecular basis of cancer. Recent work on the fly and worm homologs of the Retinoblastoma tumour suppressor (pRb) has uncovered some unexpected pRb functions: Evolutionary conserved pRb complexes participate in cell fate determination, repress germline-specific gene expression and interact with RNA interference pathways. Similar complexes appear to operate in human cells.