Cells routinely make mistakes. Some mistakes are encoded by the genome and may manifest as inherited or acquired diseases. Other mistakes occur because metabolic processes can be intrinsically inefficient or inaccurate. Consequently, cells have developed mechanisms to minimize the damage that would result if mistakes went unchecked. Here, we provide an overview of three quality control mechanisms--nonsense-mediated mRNA decay, nonstop mRNA decay, and no-go mRNA decay. Each surveys mRNAs during translation and degrades those mRNAs that direct aberrant protein synthesis. Along with other types of quality control that occur during the complex processes of mRNA biogenesis, these mRNA surveillance mechanisms help to ensure the integrity of protein-encoding gene expression.