Over the past 15 years considerable progress has been made in understanding the molecular mechanisms of mRNA decay in both prokaryotes and eukaryotes. Interestingly, unlike other important biological reactions such as DNA replication and repair, many features of mRNA decay differ between prokaryotes or eukaryotes. Even when a particular enzyme like poly(A) polymerase has been conserved, polyadenylation of mRNAs in prokaryotes appears to serve a very different function than it does in eukaryotes. Furthermore, while mRNA degrading multiprotein complexes have been identified in both prokaryotes and eukaryotes, their composition and biochemical mechanisms are significantly different. Accordingly, this review seeks to provide a concise comparison of our current knowledge regarding the pathways of mRNA decay in two model organisms, the prokaryote Escherichia coli and the eukaryote Saccharomyces cerevisiae. IUBMB Life, 56: 585‐594, 2004