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.
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.
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).
Corals, including some major extinct groups Rugosa and Tabulata, have been important reef builders through much of the Phanerozoic since the Ordovician Period. However, other organism groups, such as calcifying algae, especially members of the red algae Rhodophyta, and molluscs (especially the rudist bivalves during the Cretaceous Period) have created massive structures at various times. During the Cambrian Period, the conical or tubular skeletons of Archaeocyatha, an extinct group of uncertain affinities (possibly sponges), built reefs. Other groups, such as the Bryozoa have been important interstitial organisms, living between the framework builders. The corals which build reefs today, the Scleractinia, arose after the Permian–Triassic extinction event that wiped out the earlier rugose corals (as well as many other groups), and became increasingly important reef builders throughout the Mesozoic Era. They may have arisen from a rugose coral ancestor. Rugose corals built their skeletons of calcite and have a different symmetry from that of the scleractinian corals, whose skeletons are aragonite. However, there are some unusual examples of well-preserved aragonitic rugose corals in the late Permian. In addition, calcite has been reported in the initial post-larval calcification in a few scleractinian corals. Nevertheless, scleractinian corals (which arose in the middle Triassic) may have arisen from a non-calcifying ancestor independent of the rugosan corals (which disappeared in the late Permian).