Cancer cell-derived exosomes have recently been implicated in contributing to metastasis. It is expectable that specific membrane trafficking factors would participate in the regulation of exosome formation, transport and release from cells. Recent investigations have revealed certain members belonging to the SNARE, sorting factor and Rab GTPase protein families as being crucial in governing the exosome life cycle. These trafficking components have therefore been primed as new targets potentially modulating cancer progression. This mini-review is focused on the involvement of membrane trafficking components in regulating exosome-related transport and signaling, and in turn influencing clinical outcomes in cancer.