Depression is common in cancer patients, and the interactions between patients’ psychological and physiological experiences with cancer can pose significant ethical challenges for individual clinicians as well as health care systems. Oncological treatments can have a significant impact on patients’ mental health, while cancer patients with preexisting mental health conditions might require specialized care. The double stigma of cancer and mental illness introduces additional ethical complexities. How should physicians and other health care professionals maintain boundaries with cancer patients or integrate caregivers and surrogates into decision-making processes? What mental health screening processes should be implemented in cancer research and care settings? This month’s issue of the AMA Journal of Ethics explores these questions and underscores the need to provide empathic, well-integrated mental health care in oncology settings.