Oncology nurses and nurse practitioners often provide initial (prior to transition of care to a psychiatric provider) or maintenance assessment of and treatment for patients with depressed mood. Research informing oncology nurses and nurse practitioners on the assessment, differential diagnoses development, and treatment of depressed mood is limited. This article discusses assessment and management of common causes of depressed mood in the oncology setting. Implications for oncology nurses and nurse practitioners include improved quality of care and empowered, evidence-based clinical decision-making.