The nonsense-mediated mRNA decay (NMD) pathway is a surveillance mechanism that targets the degradation of mRNAs harboring premature termination codons (PTCs). Two key aspects of NMD are the definition of a PTC codon and the identification of the molecular machinery dedicated to this mechanism. This chapter describes the development of transgenic reporters as well as the use of genome-wide RNAi and genetic screens to identify novel components of the NMD pathway in the nematode Caenorhabditis elegans.