Lengths of the eukaryotic messenger RNA (mRNA) poly(A) tails are dynamically changed by the opposing effects of poly(A) polymerases and deadenylases. Modulating poly(A) tail length provides a highly regulated means to control almost every stage of mRNA lifecycle including transcription, processing, quality control, transport, translation, silence, and decay. The existence of diverse deadenylases with distinct properties highlights the importance of regulating poly(A) tail length in cellular functions. The deadenylation activity can be modulated by subcellular locations of the deadenylases, cis‐acting elements in the target mRNAs, trans‐acting RNA‐binding proteins, posttranslational modifications of deadenylase and associated factors, as well as transcriptional and posttranscriptional regulation of the deadenylase genes. Among these regulators, the physiological functions of deadenylases are largely dependent on the interactions with the trans‐acting RNA‐binding proteins, which recruit deadenylases to the target mRNAs. The task of these RNA‐binding proteins is to find and mark the target mRNAs based on their sequence features. Regulation of the regulators can switch on or switch off deadenylation and thereby destabilize or stabilize the targeted mRNAs, respectively. The distinct domain compositions and cofactors provide various deadenylases the structural basis for the recruitments by distinct RNA‐binding protein subsets to meet dissimilar cellular demands. The diverse deadenylases, the numerous types of regulators, and the reversible posttranslational modifications together make up a complicated network to precisely regulate intracellular mRNA homeostasis. This review will focus on the diverse regulators of various deadenylases and will discuss their functional implications, remaining problems, and future challenges.This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability