Transcriptional and epigenetic control of gene expression is critical for cell fate specification, commitment and terminal differentiation during development. However, also regulatory RNAs and RNA-binding proteins have emerged as critical developmental regulators. They control various aspects of mRNA metabolism such as stability, translation, and localization, and similar to some transcriptional regulators, such as PAX5 and MYC, they can affect gene expression on a massive scale. Consistently, defects in many mRNA regulators have been implicated in a number of human disorders, including cancer. Quaking-related (QR) proteins are conserved RNA-binding proteins of the STAR (signal transduction and activation of RNA) family. QR proteins regulate expression of diverse mRNA targets by various mechanisms, play essential roles in a whole host of developmental decisions, and function as tumor suppressors. This review discusses several best-studied members of the QR family, their developmental functions, molecular mechanisms, representative mRNA targets, and their intriguing ability to coordinately control the cell cycle and a wide range of differentiation pathways.