Botulimum neurotoxin food poisoning (botulism) has probably afflicted humankind as long as humans have preseved and stored food. In tenth-century Byzantium, blood sausage manufacture may have been banned for this reason. Botulinum preparations were suggested to Indian maharajas as a means of assassinating enemies. Botulism outbreaks in Germany in the eighteenth and nineteenth centuries led to warnings against harmful consumption of blood sausages.

In 1820, Justinus Kerner published case histories detailing the signs and symptoms of the disease we now call botulism, and postulated a biological causative agent that developed under anaerobic condition and affected the motor and autonomic nervous systems. The bacillus Clostridium botulinum was identified by van Ermengem in 1895. multiple serological subtypes were isolated in the early twentieth century, followed by identification of wound botulism in 1950, and infant botulism in 1976. Use as a bioweapon was considered in World War I. Botulinum neurotoxin type A was isolated in the 1920s. The US government investigated its deployment in World War II. After the war, clinically therapeutic formulations were prepared in the USA and Britain.