How soluble cargo molecules concentrate into budding vesicles is the subject of intensive current research. Clathrin-based vesiculation from the plasma membrane and the trans-Golgi network constitutes the best described system that supports this sorting process. Soluble ligands bind to specific transmembrane receptors which have been shown to interact directly with clathrin adaptor complexes, components of clathrin coats. At the same time, these clathrin adaptors facilitate clathrin coat assembly and probably regulate the recruitment of the rest of the coat components. Recent studies have looked at both the interaction of receptor tails with adaptors and the assembly of the clathrin coat. Progress has also been made in elucidating how soluble cargo molecules may be concentrated for exit from the endoplasmic reticulum.