Rifampin is a potent inducer of hepatic P450 oxidative enzymes. Clinically important drug interactions have been documented between rifampin and numerous other drugs, such as oral anticoagulants, oral contraceptives, cyclosporine, digitalis, and ketoconazole. New, potentially clinically significant rifampin drug interactions have been reported for haloperidol, several antiarrhythmics, fluconazole, diltiazem, and select benzodiazepines. Further research has been conducted for previously reported drug interactions with rifampin involving such drugs as glucocorticoids, cyclosporine, verapamil, and oral anticoagulants. Proper management of these interactions is essential to avoid therapeutic failures on initiating rifampin therapy and potential toxic reactions after discontinuing rifampin. New rifampin drug interactions will continue to be identified with future investigations.