Instability is a fundamental property of mRNA that is necessary for the regulation of gene expression. In E. coli, the turnover of mRNA involves multiple, redundant pathways involving 3'-exoribonucleases, endoribonucleases, and a variety of other enzymes that modify RNA covalently or affect its conformation. Endoribonucleases are thought to initiate or accelerate the process of mRNA degradation. A major endoribonuclease in this process is RNase E, which is a key component of the degradative machinery amongst the Proteobacteria. RNase E is the central element in a multienzyme complex known as the RNA degradosome. Structural and functional data are converging on models for the mechanism of activation and regulation of RNase E and its paralog, RNase G. Here, we discuss current models for mRNA degradation in E. coli and we present current thinking on the structure and function of RNase E based on recent crystal structures of its catalytic core.