Clathrin-coated vesicles (CCVs) internalize endocytosed material at the plasma membrane and also transport cargo from the trans Golgi network (TGN) to the endosome/lysosome system. Recent work has revealed details of numerous proteins involved in clathrin-mediated vesicle budding. In a Commentary on p. 9, Peter McPherson and co-workers discuss the roles of two related modules present in several of these proteins: the ENTH domain, first identified in the clathrin-binding protein epsin; and the ANTH domain, characteristic of another clathrin-binding protein, AP180. Both domains bind membrane phosphoinositides, allowing other regions of the protein to promote clathrin assembly. The binding mechanisms are different, however, and the ENTH, but not the ANTH, domain appears to be able to promote membrane curvature. ENTH/ANTH proteins might have additional functions: increasing evidence indicates that they function as cargo-specific adaptors. Moreover, the domains bind to microtubules and might thus tether clathrin-coated membranes to the cytoskeleton. The recent demonstration that ENTH/ANTH proteins can bind adaptor proteins such as AP-1 and GGA proteins is perhaps most significant, suggesting that the domains are in fact universal components of the clathrin-mediated budding machinery.