Trafficking within the exocytic and endocytic pathways of eukaryotic cells involves the generation of caged transport carriers that mediate communication between compartments through vesicle budding and fusion. Structural studies of vesicle cage structures using X-ray crystallography and cryo-electron microscopy approaches reveal new insight into cargo-dependent coat assembly mechanisms. Clathrin and coat protein complex II (COPII) use conserved primary element alpha-solenoid and WD40 structural motifs found in self-assembling cage scaffolds to generate unique geometries that sort cargo and produce vesicles. These studies emphasize molecular and structural principles that reflect the properties of self-assembling nanomachines to regulate cargo capacity in trafficking pathways.