Clathrin-coated vesicles are constantly assembling and disassembling to perform their task of transporting proteins from the outside of the cell inside. They are responsible for importing LDL cholesterol, and they play a role in breast cancer through internalization of a key receptor. During disease progression of HIV infection, clathrin-coated vesicles are subverted by a viral protein to cause down-regulation of the viral receptor CD4 in an important but not fully understood step. These molecules, and a wide range of others, are selectively trapped in the clathrin-coated vesicle for import into the cell. The new insights into how the vesicle forms help build a picture of the overall process and suggest possible targets for future therapeutic intervention.