Development and differentiation of multicellular organisms requires cell-to-cell communication. In plants direct signaling and exchange of macromolecules between cells is possible through plasmodesmata. Recently direct exchange of membrane-bound vesicles and organelles has been demonstrated between animal cells through formation of cytoplasmic bridges (tunneling nanotubes) in vitro. Here we review recent developments in cell-to-cell trafficking of macromolecules in plants and animals.