RNA interference (RNAi) is widely used in Caenorhabditis elegans to identify gene function and has been adapted as a high-throughput screening method to identify genes involved in essential processes. The technique has been applied to parasitic nematodes with variable success and we believe that inconsistent outcomes preclude its use as a robust screen with which to identify potential control targets. In this article, key issues that require clarification are discussed, including the mode of delivery of double-stranded RNA to the parasite, the developmental stage targeted and, perhaps of most importance, whether the RNAi pathway (as defined by studies in C. elegans) is fully functional in some parasitic nematodes.