In older literature, the scientific name of this species was often given as C. menisorrah. The blacktail reef shark (C. wheeleri), native to the western Indian Ocean, is now regarded as the same species as the grey reef shark by most authors. It was originally distinguished from the grey reef shark by a white tip on the first dorsal fin, a shorter snout, and one fewer upper tooth row on each side. Based on morphological characters, vertebral counts, and tooth shapes, Garrick (1982) concluded the grey reef shark is most closely related to the silvertip shark (C. albimarginatus). This interpretation was supported by a 1992 allozyme phylogenetic analysis by Lavery.
Although there are no active reef shark fisheries in the US Pacific, the reef sharks' disappearance could be caused by recreational fishing or illegal shark finning, which, combined, kill 26 million to 73 million sharks each year. Another possible explanation is that the reef sharks are starving. Their food sources, including coral reef fishes, are decreasing in number because of habitat destruction and human exploitation, and could be taking the sharks with them.
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.
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).