In current models, ribosome release from the endoplasmic reticulum (ER) is coupled to the termination of protein translation. Thus, coincident with termination, membrane-bound ribosomes dissociate into their component subunits and are released into the cytosol. Here, we review past and current data and propose that the affinity of the ribosome for the ER membrane is decreased during translation, with ribosome release occurring when a membrane-bound ribosome is engaged in the synthesis of a protein lacking a signal sequence. Our model emphasizes a role for the conformation of the large ribosomal subunit in the regulation of membrane affinity and provides a mechanism for translation-coupled ribosome release.