The Caribbean Reef Shark is known to become aggressive in the presence of food, but they are mostly only considered dangerous to humans because of its size. This shark was fished in Belize for almost the entire 20th century. They were used to make local delicacies in addition to liver oil (mostly used in cosmetics). Their low reproduction rate combined with a high level of hunting and fishing have caused the numbers to dwindle. The shark is now considered to be near threatened. Many countries and organizations have banned the commercial fishing of this species.
Along with the blacktip reef shark (C. melanopterus) and the whitetip reef shark (Triaenodon obesus), the grey reef shark is one of the three most common sharks inhabiting Indo-Pacific reefs. They actively expel most other shark species from favored habitats, even species larger in size. In areas where this species co-exists with the blacktip reef shark, the latter species occupies the shallow flats, while the former stays in deeper water. Areas with a high abundance of grey reef sharks tend to contain few sandbar sharks (C. plumbeus), and vice versa; this may be due to their similar diets causing competitive exclusion.