Khat chewing is deeply rooted in the daily life of people living in the Horn of Africa and South Arabia. Three decades of experimental and clinical research on khat has provided clear documentation of its pharmacological and toxicological effects. Cathinone has been identified as its main active compound, which is the only amphetamine-like drug so far isolated from a botanic source. Studies that have used experimental models of drug addiction clearly show cathinone and, to a lesser extent, cathine as responsible for the reinforcing effects that induce and maintain a khat-chewing habit. Since chewing as a means of consumption is necessarily slow, the amount of active principles absorbed is restricted and the onset of the rewarding effects is delayed. This impedes khat dependence, keeping it at the mild levels observed in experienced chewers. Cathinone may also account for mental disturbance observed in some chronic khat chewers. Adverse mental effects have been noticed mostly when khat has been linked to stressful settings or events. Several recent studies that have focused on the general toxicology of khat have shown that the habit may have detrimental health consequences when associated with unhealthy lifestyles, although there is no evidence that khat chewing increases the incidence of specific organic diseases. Moreover, smoking and alcohol use may interact with irritant active principles of khat, such as terpenoids and tannins, in causing displasic lesions of oral and esophageal mucosa, facilitating the development of cancer. No therapeutic effects have yet been found for khat. 42 references