The completion of the Caenorhabditis elegans genome sequence was the initial step toward the use of whole-genome analysis in this model organism. Advances in C. elegans genomics include transcript profiling, gene-function screens using RNA-mediated interference, and protein-interaction mapping using the yeast two-hybrid system. Recent reports have employed these methods to gain new insights into diverse biological problems such as tissue-specific gene expression, cell-fate specification, genome organization, the DNA damage response, and early embryonic development. These studies combined genomic approaches to probe complex biological pathways on an unprecedented scale.