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The rising global availability of the stimulant and euphoric substances, khat and synthetic cathinones, has become a cause for concern in many countries, including the United States. Both substances are illegal in United States, although this has not deterred their use. Besides central nervous system effects, these drugs also cause sympathomimetic and orodental adverse effects, similar to those of amphetamine. Although synthetic cathinones are stronger than khat in most cases, the latter additionally contains tannins, which have astringent effects on tissues components, including those in the oral cavity. Recognizing the use prevalence and reported orodental adverse effects of khat and synthetic cathinones, dental practitioners should be more familiar with these substances to optimally treat and educate their patients abusing them. This paper reviews the pharmacology and adverse effects of khat and synthetic cathinones, along with the extent of their use in United States, with particular emphasis on dental implications.