The processing and subcellular trafficking of seed storage proteins is a critical area of physiological, agricultural and biotechnological research. Trafficking to the lytic vacuole has been extensively discussed in recent years, without substantial distinction from trafficking to the protein storage vacuole (PSV). However, despite some overlap between these pathways, there are several examples of unique processing and machinery in the PSV pathway. Moreover, substantial new data has recently come to light regarding the important players in this pathway, in particular, the intracellular NHX proteins and their role in regulating lumenal pH. In some cases, these new data are limited to genetic evidence, with little mechanistic understanding. As such, the implications of these data in the current paradigm of PSV trafficking is perhaps yet unclear. Although it has generally been assumed that the major classes of storage proteins are trafficked via the same pathway, there is mounting evidence that the 12S globulins and 2S albumins may be trafficked independently. Advances in identification of vacuolar targeting signals, as well as an improved mechanistic understanding of various vacuolar sorting receptors, may reveal the differences in these trafficking pathways.