The use by the Khoisan of South Africa of Sceletium plants in psychoactive preparations has often been alluded to in the literature. However, much of it is fragmentary and contradictory. The current review reassembles the historical data recorded over a 300-year period, describes techniques for the preparation and use of "kougoed' from plants of Sceletium and documents the subjective experiences of a number of contemporary users. Apart from chewing the dried product, after "fermentation', there are reports of uses as tinctures for sedation and analgesia, chewing the material directly and smoking the residue after chewing. The symbolic connections of Sceletium with eland antelopes, the "trance animals' par excellence of the San hunter-gatherers is noted. Observations by Paterson (1789) and reports of contemporary users indicate a synergism and potentiation with smoked Cannabis. There is no evidence to support the view that "kougoed' or Sceletium alkaloids are hallucinogenic. The alkaloid distribution in Sceletium and other members of the family Mesembryanthemaceae are considered. Chemical studies have indicated as many as nine alkaloids in Sceletium which fall into three distinct structural categories. Mesembrine, the alkaloid first isolated and named is not the dominant constituent of plants and is weakly narcotic. Evidence is assembled to suggest that traditional and contemporary methods of preparation serve to reduce levels of potentially harmful oxalates, which are found in Sceletium and other Mesembryanthemaceae. It is concluded that there is a need for further pharmacological studies on these alkaloids, based on their narcotic-anxiolytic properties, strong synergism with other psychomimetics, moderate toxicity and anti-cancer activity.