The mRNA decay rate (half-life) is a major determinant of mRNA abundance in organisms from bacteria to mammals. mRNA levels can fluctuate many-fold following a change in mRNA half-life, without any change in transcription, and these fluctuations affect how a cell grows, differentiates and responds to its environment. The half-lives of many mRNAs vary tenfold or more in response to cytokines, hormones, starvation, hypoxia, or viral infection. Three major questions regarding mRNA stability are currently being addressed. What sequences in mRNAs determine half-lives? What enzymes degrade mRNAs? What (trans-acting) factors regulate mRNA stability and how do they function? This review focuses on RNA-binding or regulatory proteins and on candidate messenger ribonucleases (mRNases).