siRNA screens have been used for gene discovery in a wide range of cellular and organism contexts. Many of the lessons learnt from some of the initial problems have been used to develop further practices and validation methods. RNAi screens have not only determined potential genes involved in basic biological processes, but they have become a tool used to dissect out key elements of disease or avenues of novelty in treatments. In my presentation, I will present some different assays we have used, to showcase the potential use of siRNA as part of the gene discovery process, and highlight the precautions we have taken to maintain reliability.