BACKGROUND The increasing number and complexity of oral agents for cancer (OACs) have created a paradigm shift in the process and outcomes in oncology care. With 25%-30% of new oncology medications in development being oral agents, and a steady increase in approvals in the past 5-10 years, the issues are relevant in clinical practice. OBJECTIVES The purpose of this article is to provide an overview of the challenges related to OACs, including adherence, and to describe the consequences of adherence and resources for oncology nurses. METHODS The literature was searched to determine challenges related to OACs and their impact on adherence, and an overview of the issues was compiled. FINDINGS Oncology nurses are key stakeholders in recognizing the challenges and issues associated with the change in treatment regarding OACs. Oncology nurses are an integral part of managing the oral agent process, from access to adherence. Oncology nurses need to understand the issues surrounding OACs so that adherence practices can be improved.