Juvenile Caribbean reef sharks are preyed upon by larger sharks such as the tiger shark (Galeocerdo cuvier) and the bull shark (C. leucas). Few parasites are known for this species; one is a dark variegated leech often seen trailing from its first dorsal fin.[4] Off northern Brazil, juveniles seek out cleaning stations occupied by yellownose gobies (Elacatinus randalli), which clean the sharks of parasites while they lie still on the bottom.[10] Horse-eye jacks (Caranx latus) and bar jacks (Carangoides ruber) routinely school around Caribbean reef sharks.[11]

The Caribbean reef shark is the most common shark on or near coral reefs in the Caribbean. It is a tropical inshore, bottom-dwelling species of the continental and insular shelves. Although C. perezi mainly inhabits shallow waters, it has been recorded to reach depths to at least 98 feet (30 m). Caribbean reef sharks are commonly found close to drop-offs on the outer edges of coral reefs and also may lie motionless on the bottom of the ocean floor. This phenomenon has also been observed in caves off the coast of Mexico and off the Brazilian archipelago of Fernando de Noronha.
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.
Grey reef sharks feed mainly on bony fishes, with cephalopods such as squid and octopus being the second-most important food group, and crustaceans such as crabs and lobsters making up the remainder. The larger sharks take a greater proportion of cephalopods.[20] These sharks hunt individually or in groups, and have been known to pin schools of fish against the outer walls of coral reefs for feeding.[14] Hunting groups of up to 700 grey reef sharks have been observed at Fakarava atoll in French Polynesia.[21][22] They excel at capturing fish swimming in the open, and they complement hunting whitetip reef sharks, which are more adept at capturing fish inside caves and crevices.[4] Their sense of smell is extremely acute, being capable of detecting one part tuna extract in 10 billion parts of sea water.[13] In the presence of a large quantity of food, grey reef sharks may be roused into a feeding frenzy; in one documented frenzy caused by an underwater explosion that killed several snappers, one of the sharks involved was attacked and consumed by the others.[23]

Reef sharks play a major role in shaping Caribbean reef communities.  As the top predators of the reef and indicator species for marine ecosystems, they help maintain the delicate balance of marine life in reef environments.  Reef sharks are highly valued for their meat, leather, liver oil, and fishmeal, which make them prone to overfishing and targeting. Yet, their importance for the tourism industry makes them more valuable alive than dead. In 2011, Honduras declared its waters to be a permanent sanctuary for sharks, making fishing for these species completely forbidden.
Off Enewetak, grey reef sharks exhibit different social behaviors on different parts of the reef. Sharks tend to be solitary on shallower reefs and pinnacles. Near reef drop-offs, loose aggregations of five to 20 sharks form in the morning and grow in number throughout the day before dispersing at night. In level areas, sharks form polarized schools (all swimming in the same direction) of around 30 individuals near the sea bottom, arranging themselves parallel to each other or slowly swimming in circles. Most individuals within polarized schools are females, and the formation of these schools has been theorized to relate to mating or pupping.[25][26]
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.