The development of numerous oral chemotherapy agents has led to a new paradigm in cancer treatment. Oral chemotherapy can be self-administered conveniently, so patients with cancer can receive their treatments in their homes instead of in a supervised and controlled healthcare environment. Cancer now is recognized as a treatable chronic disease, and new oral chemotherapy agents have been developed that offer targeted cancer treatment. Although the newer oral chemotherapy agents offer additional treatment options, they also pose challenges for patients and healthcare providers. Patient adherence and monitoring can be challenging, and reimbursement issues abound. Oncology nurses play a key role in assessing, educating, and monitoring patients receiving oral chemotherapy. In addition, they may be involved in assisting patients with obtaining reimbursement and, in some cases, may be instrumental in locating patient assistance programs. This article discusses patient care issues related to treatment with oral chemotherapy agents and provides a historical overview of their development and use.