Disease and disorders of the central nervous system (CNS) are some of the most common ailments afflicting mankind, and it has been estimated that 32% of the population of the USA suffers from a disorder of the brain once in a lifetime, and 15% of the population over 18 suffer a mental disorder at least monthly. The use of natural products as psychotropic agents to alleviate mental disorders, or to create altered mental states, probably dates back to the dawn of time, when the first trial-and-error experiments by shamans or other experimenters led to the discovery of the effect of certain plant extracts on the mind. It is thus significant that the first alkaloid to be purified from a plant was the psychoactive analgesic morphine. Although there is extensive literature on the use of plants and plant extracts as hallucinogenic agents, the search for natural products for therapeutic psychotropic purposes is much less well-developed than, for example, the search for anticancer agents. Nevertheless, there are enough examples of the successful search for useful naturally-occurring psychotropic agents to ensure that a continued search is likely to be productive. This review will summarize results in the discovery of CNS-active natural products, with an emphasis on compounds that may be useful for therapeutic purposes.