Messenger ribonucleic acid (mRNA) decay is an important cellular mechanism for regulating gene expression in both bacteria and eukaryotes. The enzymes involved and the factors that modulate their activity have been well-characterized. Enzymes responsible for mRNA turnover attack either the 5¢ or 3¢ ends (exoribonucleases) or cleave the RNA in the middle (endoribonucleases). Transcripts generally have specific modifications at their ends, such as the 5¢ cap and 3¢ poly(A) tail in eukaryotes, to protect them from exonucleolytic decay. RNA-binding proteins can modulate decay rates by recruiting mRNA degradation enzymes or by altering messenger ribonucleoprotein (mRNP) conformation to favour or impede decay. Here, we describe the enzymes and regulatory factors of the mRNA decay pathways in bacteria and eukaryotes, highlighting similarities between the two. We also discuss how mRNA degradation is regulated by RNA-binding proteins, and how mRNA turnover pathways are used to identify and degrade aberrant mRNAs.