Background: Ciguatera fish poisoning (CFP) is the most common poisoning from seafood consumption with an estimated 50,000 cases per year worldwide. Attention to this malady in the English language literature has grown over the past five decades. Endemic areas include the South Pacific Ocean and the Caribbean Sea. It is likely that CFP has been present since ancient times, but records to substantiate this are scarce. Objective: This historical review looks for clues in earlier writings about potential encounters with CFP as Europeans sailed farther from home into these endemic regions with little idea of what awaited them. We divide these records into the Age of Discovery and the Age of Enlightenment. Methods: Review of available historical texts written by or about early European explorers with descriptions of illness attributed to eating fish. Results: Fish poisonings appear in translated writings of early Spanish and Portuguese explorers in the 1500s, the writings of Captain James Cook’s voyages to the South Pacific, and in Captain William Bligh’s fateful voyage after the Mutiny on the Bounty. The most credible description of CFP comes from an early author in the Spanish colony of Cuba in the late 1700s. Conclusions: Although the quality of the observations varies, Parra in Cuba likely experienced CFP. Plausible CFP for Cook in the South Pacific and Locke in the Bahamas as both have elements of CFP. The descriptions from Quiros, Anghira, and Bligh lack sufficient detail to verify or to refute completely the possibility of CFP.