Genotoxic stress leads to DNA damage which can be detrimental to the cell. A wellorchestrated cellular response is mounted to manage and repair the genotoxic stressinduced DNA damage. Our understanding of genotoxic stress response is derived mainly from studies focused on transcription, mRNA splicing, and protein turnover. Surprisingly not as much is understood about the role of mRNA translation and decay in genotoxic stress response. This is despite the fact that regulation of gene expression at the level of mRNA translation and decay plays a critical role in a myriad of cellular processes. This review aims to summarize some of the known findings of the role of mRNA translation and decay by focusing on two categories of examples. We discuss examples of mRNA whose fates are regulated in the cytoplasm and RNA-binding proteins that regulate mRNA fates in response to genotoxic stress.