Khat chewing is deeply rooted in the culture and tradition of communities in khat belt countries, and its consumption is spread to other countries through the suitcase trade. The aim of this article is to review current knowledge on the chemistry, social, pharmacology and toxicology of khat and its use. Khat produces effect invariably in every system, which is harmful or beneficial in some instances. Harmful effects are observed in heavy users, although firm evidence is lacking. Chewing khat acutely elicits states of euphoria, which is followed by low mood. Khat contains alkaloids with psychostimulant properties, but the effect cannot be totally explained by these alkaloids. It is also not clear whether the effect produced in some organs like liver could be attributed to khat or pesticides sprayed during farming. Although the evidence indicates that khat has adverse effects in most organs, our understanding of the complex interaction between use and effect is incomplete, and causal relationships have not yet been described. Moreover, khat has positioned itself well in the social, economic and political arena. Thus, a multidisciplinary research is required to understand the different dimensions and come up with ways that maximize the benefit while minimizing the risk. Copyright © 2017 John Wiley & Sons, Ltd.