Cell survival depends on the precise and correct production of polypeptides. Eukaryotic cells have evolved conserved proofreading mechanisms to get rid of incomplete and potentially deleterious proteins. The nonsense-mediated mRNA decay (NMD) pathway is an example of a surveillance mechanism that monitors premature translation termination and promotes degradation of aberrant transcripts that code for nonfunctional or even harmful proteins. In this review we will describe our current knowledge of the NMD pathway, analyzing primarily the results obtained from the yeast Saccharomyces cerevisiae, but establishing functional comparisons with those obtained in higher eukaryotes. Based on these observations, we present two related working models to explain how this surveillance pathway recognizes and selectively degrades aberrant mRNAs.