The level of an MRNA in the cytoplasm represents a balance between the rate at which the mRNA precursor is synthesized in the nucleus and the rates of nuclear RNA processing and export and cytoplasmic mRNA degradation. Although most studies of gene expression have focused on gene transcription and its control, a great deal of information indicates that mRNA degradation and its regulation are major control mechanisms that help govern cellular mRNA levels. The objective of this chapter is not to exhaustively review our present knowledge in the area of eukaryotic mRNA degradation, but to provide a short general discussion of the importance of mRNA degradation and its regulation and a brief overview of recent findings and present knowledge. The overview is followed by a more in-depth discussion of one of the several pathways for mRNA degradation. We concentrate on the pathway for regulated mRNA degradation mediated by mRNA-binding proteins and endonucleases that cleave within the body of mRNAs. As a potential example of this type of control, we focus on the regulated degradation of the egg yolk precursor protein vitellogenin on the mRNA-binding protein vigilin and the mRNA endonuclease polysomal ribonuclease 1 (PMR-1).