Oral chemotherapy is assuming an increasingly important role in cancer therapy. Pharmaceutical firms continue to invest heavily in oral drug development with approximately 25% of more than 400 antineoplastic drugs currently in the development pipeline planned as oral agents. New treatments, patient preference, and the economic realities of cancer care delivery present physicians, nurses, pharmacists, and cancer center administrators with a challenge to restructure and reorganize to provide cost-effective and high-quality care to cancer patients. Oncology nurses are uniquely positioned to step into new roles emphasizing patient and family education and support. A discussion of the Health Belief Model provides an increased understanding of patient motivation and helps healthcare providers increase compliance among patients using oral therapies. This article provides an overview of the current status of oral cancer therapy in the United States and takes into consideration a historical perspective; illustrates pharmacology, indications, administration, and side effect profile through an exemplar agent; discusses potential advantages of and challenges to integration of oral therapies; and discusses alternative methods of patient and family education to improve compliance and outcome.