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.
Caribbean reef sharks are prohibited from being caught by commercial fishers in U.S. waters, however harvest of these sharks may be permissible in other countries. During the past few decades, an increasingly popular (and even more controversial) commercial aspect of the Caribbean reef shark has emerged. To increase clientele, many dive-boat operations have come to include shark-feeding dives as a part of their agenda, with some of the most popular sites being main habitats of Caribbean reef sharks. Although new regulations prohibit such feedings off the coast of Florida, no such restrictions have been placed on operations in Bahamian or other Caribbean waters.