Highlights • EVs contribute to numerous pathological problems associated with cancer. • EVs from noncancerous cells play parts in normal communication between cells. • Blocking all EV release in the body could cause as many problems as it prevents. • Hypoxia, a feature of solid tumours, contributes to EV release, contents and activity. • Targeting hypoxia should inhibit EVs and their influences in cancer. Increasing evidence indicates that extracellular vesicles (EVs) are key players in undesirable cell–cell communication in cancer. However, the release of EVs is not unique to cancer cells; normal cells release EVs to perform physiological roles. Thus, selective inhibition of EV release from cancer cells is desirable. Hypoxia contributes to tumour development and aggressiveness. EV quantities and thus undesirable communications are substantially increased in hypoxia. Targeting hypoxia could selectively inhibit EV release from tumour cells without disturbing physiologically relevant EVs. The unfavourable association between hypoxia and EV release is evident in multiple tumour types; therefore, targeting hypoxia could have a broad therapeutic benefit.