Within the last decade the hitherto little known psychoactive substance of khat has emerged as a regional and international issue. In the Horn of Africa khat production has spurred an economic boom, but dramatic increases in consumption have raised public health concerns. Given the complexity of the topic spanning multiple academic disciplines and fields of professional practice, the need for a systematic overview is urgent. To facilitate the exchange of information, prompt interdisciplinary research and alert international organisations and governments, the authors organised an international and interdisciplinary khat conference in 2009. This special issue of the Journal of Ethnopharmacology contains articles written by different conference speakers that present the current state of knowledge and the challenges for future research and politics.