Technical Abstract: The reaction chemistry pertaining to gossypol, a toxic pigment found in cottonseed is critically reviewed. Gossypol has been known for well over a hundred years and the dichotomy between its toxicity to man and nonruminant animals and its unique biological activities as antifertility, anticancer, and plant defense agent places gossypol in an unusual position. On one hand researchers are currently working diligently to produce glandless strains of cottonseed devoid of gossypol to provide high quality cottonseed products without the gossypol’s associated toxicity. In contrast, researchers are using gossypol’s binaphthyl structure, functionality, and unique biological activities to make gossypol a potentially important value-added natural product. The research to understand gossypol’s reaction chemistry, in conjunction with reports on gossypol’s antifertility and anticancer properties, has opened future research opportunities for gossypol research and its utilization.