Grey reef sharks are prey for larger sharks, such as the silvertip shark. At Rangiroa Atoll in French Polynesia, great hammerheads (Sphyrna mokarran) feed opportunistically on grey reef sharks that are exhausted from pursuing mates. Known parasites of this species include the nematode Huffmanela lata and several copepod species that attach to the sharks' skin, and juvenile stages of the isopods Gnathia trimaculata and G. grandilaris that attach to the gill filaments and septa (the dividers between each gill).
This species is taken by commercial and artisanal longline and gillnet fisheries throughout its range. It is valued for meat, leather, liver oil and fishmeal. The Caribbean reef shark is the most common shark landed in Colombia (accounting for 39% of the longline catch by occurrence), where it is utilized for its fins, oil and jaws (sold for ornamental purposes). In Belize, this species is mainly caught as bycatch on hook-and-line intended for groupers and snappers; the fins are sold to the lucrative Asian market and the meat sold in Belize, Mexico, and Guatemala to make "panades", a tortilla-like confection. A dedicated shark fishery operated in Belize from the mid-1900s to the early 1990s, until catches of all species saw dramatic declines. The flesh of this species may contain high levels of methylmercury and other heavy metals.
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Most observed displays by grey reef sharks have been in response to a diver (or submersible) approaching and following it from a few meters behind and above. They also perform the display towards moray eels, and in one instance towards a much larger great hammerhead (which subsequently withdrew). However, they have never been seen performing threat displays towards each other. This suggests the display is primarily a response to potential threats (i.e. predators) rather than competitors. As grey reef sharks are not territorial, they are speculated to be defending a critical volume of "personal space" around themselves. Compared to sharks from French Polynesia or Micronesia, grey reef sharks from the Indian Ocean and western Pacific are not as aggressive and less given to displaying.