Currently, 10% of cancer chemotherapy is prescribed to patients by means of an oral formulation, but, by 2013, this percentage is predicted to increase to 25%. Oral chemotherapy offers many advantages, including no need for sometimes painful intravenous access, no intravenous drug administration fees, more time at home for patients, and a greater sense of patient autonomy. However, oral cancer chemotherapy also poses challenges, many of which revolve around adherence and safety. These challenges are discussed here. There are few other circumstances in which patient education and the maintenance of institutional safety infrastructure play such an integral role in sustaining favorable cancer clinical outcomes.