Most membrane-associated proteins need sophisticated guidance systems to help them find their way to the right subcellular compartment. The mechanism of post-translational targeting to the endoplasmic reticulum (ER) is particularly elusive; so, to try to identify the components involved, Stephen High and colleagues have been studying tail-anchored (TA) proteins (p. 1743). These are a diverse class of membrane-associated proteins characterised by a hydrophobic C-terminal sequence. The researchers focused on a model ER-associated TA protein, Sec61β, whose targeting to the ER is ATP dependent. Using crosslinking agents, they found that Sec61β binds to the molecular chaperone Hsc70, and that this binding depends on the hydrophobic TA sequence. When the researchers mixed together combinations of purified components normally present in the cytosol, they found that Hsc70 and its co-chaperone Hsp40 are sufficient to target and integrate Sec61β into the ER. The researchers compare the kinetics ofthis system with other pathways of TA-protein biogenesis and conclude that the Hsc70-Hsp40 system is an important mediator of post-translational integration for TA proteins.