mRNAs carrying premature termination codons are targeted for degradation by the nonsense-mediated decay (NMD) pathway. Previous work had suggested that in mammals NMD is restricted to the pioneer round of translation and thus to transcripts bound to the cap-binding complex (CBC). This would suggest that mRNAs associated with the eukaryotic translation initiation complex eIF4F (which replaces the CBC after export of mature transcripts to the cytoplasm) are immune to this pathway. Two studies have used various approaches to test this theory in human cells. Both groups observed that transcripts associated with eIF4E (the cap-binding component of eIF4F) were susceptible to NMD, and that their degradation kinetics were comparable to that observed with CBC-bound mRNAs. So, it seems that NMD can target mRNAs that are actively being translated in human cells, which is consistent with previous observations in yeast.