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.
Caribbean reef sharks are sometimes seen resting motionless on the sea floor or inside caves; it is the first active shark species in which such a behavior was reported. In 1975, Eugenie Clark investigated the famed "sleeping sharks" inside the caves at Isla Mujeres off the Yucatan Peninsula, and determined that the sharks were not actually asleep as their eyes would follow divers. Clark speculated that freshwater upwellings inside the caves might loosen parasites on the sharks and produce an enjoyable "narcotic" effect. If threatened, Caribbean reef sharks sometimes perform a threat display, in which they swim in a short, jerky fashion with frequent changes in direction and repeated, brief (1–1.2 second duration) drops of the pectoral fins. This display is less pronounced than the better-known display of the grey reef shark (C. amblyrhynchos).
Based on morphological similarities, Jack Garrick in 1982 grouped this species with the bignose shark (C. altimus) and the sandbar shark (C. plumbeus), while Leonard Compagno in 1988 placed it as the sister species of the grey reef shark (C. amblyrhynchos). A phylogenetic analysis based on allozyme data, published by Gavin Naylor in 1992, indicated that the Caribbean reef shark is the sister taxon to a clade formed by the Galapagos shark (C. galapagensis), dusky shark (C. obscurus), oceanic whitetip shark (C. longimanus), and the blue shark (Prionace glauca). However, more work is required to fully resolve the interrelationships within Carcharhinus.
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One useful definition distinguishes reefs from mounds as follows: Both are considered to be varieties of organosedimentary buildups – sedimentary features, built by the interaction of organisms and their environment, that have synoptic relief and whose biotic composition differs from that found on and beneath the surrounding sea floor. Reefs are held up by a macroscopic skeletal framework. Coral reefs are an excellent example of this kind. Corals and calcareous algae grow on top of one another and form a three-dimensional framework that is modified in various ways by other organisms and inorganic processes. By contrast, mounds lack a macroscopic skeletal framework (see stromatolite). Mounds are built by microorganisms or by organisms that don't grow a skeletal framework. A microbial mound might be built exclusively or primarily by cyanobacteria. Excellent examples of biostromes formed by cyanobacteria occur in the Great Salt Lake in Utah, and in Shark Bay on the coast of Western Australia.