The regulated phosphorylation and de-phosphorylation of the alpha subunit of translation initiation factor 2 (eIF2) potently regulates global and gene-specific mRNA translation and thereby broadly affects proteostasis in diverse physiological and pathological settings. Phosphorylated eIF2 is a convergence point for several stress response pathways and its downstream effector processes are known as the integrated stress response (or ISR). In this talk I will review recent advances in our understanding of the ISR and its role in proteostasis.