This chapter examines the plant- and animal-based poisons used for hunting by indigenous San (“Bushmen”) of southern Africa. The San are iconic hunter-gatherers, but their lifestyle is threatened by modernity. Poisons are one key element in the San bow and arrow hunting, a symbiotic technology comprising multiple innovative components that are required to work together to perform a desired task. Making poisons reflects profound knowledge of the environment, its resources, and some basic pharmacological understanding of key ingredients. The plant poisons are mainly cardiac glycosides, whereas the animal poisons are commonly cytotoxic and neurotoxic. Studying San hunting techniques and poisons can increase understanding of the past hunting practices of early humans in Africa and provide insights into the levels of cognition and decision-making capabilities of hominins. The San pharmacopeia has yielded beneficial biomolecules for health conditions and may provide many more in the future. Keywords: Ethnobiology, hunting, toxicants, neurotoxin, phytotoxin, insects.