Triazole drugs are widely used in cancer patients for prophylaxis and treatment of life-threatening invasive fungal infections. Fluconazole, available for over two decades, is safe and effective in patients with cancer; however, the excellent safety profile of fluconazole may not be applicable to the newer triazoles. Itraconazole, voriconazole and posaconazole are associated with adverse events, and drug interactions frequently occur, particularly in cancer patients, since the triazoles and many drugs used in cancer chemotherapy are metabolized via a common metabolic pathway, the hepatic cytochrome P450 system. Close monitoring for drug interactions is needed when triazoles are used with anti-neoplastic drugs and dosage modification of the triazole or its discontinuation may be required. Monitoring of triazole serum concentrations is becoming an important aspect of management to minimize toxicity and ensure efficacy.