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.
The Caribbean reef shark is a viviparous species, meaning its developing embryos are nourished via a placental connection. The litters average four to six pups. Although this shark’s reproduction has not been studied in the northern hemisphere, but to the south, parturition occurs during the Amazon summer of November to December. Pregnant females are often found to have biting scars from males on the sides of their bodies, due to the aggressive behaviors of males during mating. Gestation is believed to take approximately one year. A pregnant female with biting scars and wounds on the sides of her body, taken off the coast of north-northeastern Brazil, carried four near-term embryos. One was a 27.5 in. (700 mm) long male and three were females measuring 27.0 in. (685 mm), 27.4 in. (697 mm), and 27.7 in. (704 mm) in length. Because she was carrying near-term embryos, it is postulated that this area may be a pupping ground. Although such captures have shed light on the topic, relatively little is known about the reproduction of the Caribbean reef shark. Much information has been obtained from a pregnant female carrying four near-term embryos off the coast of northeastern Brazil. This female had scars and wounds on her side. Because the shark carried near-term embryos, it is postulated that this area may be a pupping ground.
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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Grey reef sharks are often curious about divers when they first enter the water and may approach quite closely, though they lose interest on repeat dives. They can become dangerous in the presence of food, and tend to be more aggressive if encountered in open water rather than on the reef. There have been several known attacks on spearfishers, possibly by mistake, when the shark struck at the speared fish close to the diver. This species will also attack if pursued or cornered, and divers should immediately retreat (slowly and always facing the shark) if it begins to perform a threat display. Photographing the display should not be attempted, as the flash from a camera is known to have incited at least one attack. Although of modest size, they are capable of inflicting significant damage: during one study of the threat display, a grey reef shark attacked the researchers' submersible multiple times, leaving tooth marks in the plastic windows and biting off one of the propellers. The shark consistently launched its attacks from a distance of 6 m (20 ft), which it was able to cover in a third of a second. As of 2008, the International Shark Attack File listed seven unprovoked and six provoked attacks (none of them fatal) attributable to this species.