Isoniazid inhibits the metabolism of several drugs, resulting in clinically significant interactions in some patients. Clinical trials and case reports have documented that isoniazid can cause increased phenytoin and carbamazepine serum concentrations and toxicity. In relatively high doses, isoniazid can also cause increased effect of theophylline and warfarin. Isoniazid inhibits metabolism of selected benzodiazepines and vitamin D. Inhibition of monoamine oxidase and histaminase by isoniazid can cause significant drug-food interactions. Food greatly decreases isoniazid bioavailability. Although probably best recognized as an inhibitor of drug metabolism, isoniazid has a biphasic effect of inhibition-induction on one cytochrome P450 isozyme, CYP2E1, which partially explains the interaction with acetaminophen and increased risk of hepatotoxicity. Continued investigations will likely result in discovery of new isoniazid interactions.