In Caenorhabditis elegans, the forkhead protein DAF‐16 transduces insulin‐like signals that regulate larval development and adult lifespan. To identify DAF‐16‐dependent transcriptional alterations that occur in a long‐lived C. elegans strain, we used cDNA microarrays and genomic analysis to identify putative direct and indirect DAF‐16 transcriptional target genes. Our analysis suggests that DAF‐16 action regulates a wide range of physiological responses by altering the expression of genes involved in metabolism, energy generation and cellular stress responses. Furthermore, we observed a large overlap between DAF‐16‐dependent transcription and genes normally expressed in the long‐lived dauer larval stage. Finally, we examined the in vivo role of 35 of these target genes by RNA‐mediated interference and identified one gene encoding a putative protease that is necessary for the daf‐2 Age phenotype.