The process of protein secretion is intimately linked to the rate and potential of proper folding and assembly of secretory proteins. The efficiency of protein folding is communicated to the cytoplasm via several signal transduction pathways. This regulates the rate of polypeptide chain synthesis and induction of genes encoding functions that reduce protein-folding load on the endoplasmic reticulum (ER). This review summarizes recent insights into the mechanisms that couple protein translation with protein folding in the ER.