Significance This study uncovers a critical role for a general translation factor in specific developmental stages, including immature oocytes and ES cells, and during growth-factor deprivation of mammalian cells, which induces the transition to cell-cycle arrest. These conditions alter and decrease general translation yet maintain ongoing translation. We reveal upregulation of the eukaryotic translation factor 5B (eIF5B), which becomes essential for general translation, specifically in these conditions. Importantly, our data demonstrate that eIF5B controls these cell-cycle transition and developmental stages, promoting oocyte maturation and inhibiting cell-cycle arrest. These findings underscore the importance of translational regulation in cell-cycle transitions and development.