Reverse genetics in Caenorhabditis elegans has had an enormous boost in the last decade. From the mere ability to inactivate genes and make transgenic animals in the late 1980s or early 1990s, this field has evolved to genome wide approaches that aim to inactivate all C. elegans genes and determine all expression patterns. Since this luxury position has not yet been attained, we still have to go through these experiments ourselves. Two different approaches exist to inactivate genes in C. elegans. One approach uses PCR to select for deletions in the gene of interest. Deletions can be generated using transposons or chemical mutagenesis. An alternative, or rather complementary, technique inactivates genes through RNA interference (RNAi). In this review I will describe these techniques and discuss their advantages and disadvantages. Finally, I will give an update on the current status of the genomic knockout projects.