Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes. Examples of well-documented, clinically significant interactions include warfarin, oral contraceptives, cyclosporine, glucocorticoids, ketoconazole, theophylline, quinidine, digitoxin, and verapamil. Recent reports have demonstrated clinically relevant interactions with protease inhibitors, zidovudine, delavirdine, itraconazole, nifedipine, midazolam or triazolam, nortriptyline, and doxycycline. To avoid reduced therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Enhanced knowledge of known interactions will continue to develop, including research on induction of specific cytochrome P-450 isoenzymes. New rifampin interactions will be discovered with further investigations.