Removal of the mRNA 5′ cap is an important step in the regulation of mRNA stability. mRNAs are degraded by at least two distinct exonucleolytic decay pathways, one from the 5′ end, and the second from the 3′ end. Two major cellular decapping enzymes have been identified, and each primarily functions in one of the two decay pathways. The Dcp2 decapping enzyme utilizes capped mRNA as substrate and hydrolyses the cap to release m7GDP (N7-methyl GDP), while a scavenger decapping enzyme, DcpS, utilizes cap dinucleotides or capped oligonucleotides as substrate and releases m7GMP (N7-methyl GMP). In this review, we will highlight the function of different decapping enzymes and their role in mRNA turnover.