Use of oral chemotherapy or targeted agents is shifting how cancer treatment is administered, moving it from supervised office visits to self-administration at home. This study examines issues related to overadherence to oral agents that were noted during a trial conducted by the authors comparing an automated voice system to strategies to reduce symptom severity and improve adherence. Overadherence to oral agents may be a significant clinical problem, occurring more often in patients with complex dosing regimens, and may lead to increased symptom severity from side effects of treatment. Avoiding overadherence may be important for the reduction or prevention of symptoms and potentially life-threatening toxicity. Nurses need to discuss with their patients the importance of the timing of the administration of their oral oncolytic regimen, as well as to provide prompts to assist in self-administration as prescribed so that overadherence can be avoided.