Anxiety, depression, and delirium are common symptoms experienced by patients with serious illness. In palliative care, anxiety and depression commonly arise from fear of death, loss of independence, fear of being a burden to others, hopelessness, and loneliness, in addition to concern about symptom burden and disease progression. Anxiety manifests itself in four ways: physical symptoms, affective symptoms, behavioral responses, and cognitive responses. The patient and the family should be reassured that symptoms of depression and anxiety are effectively treated most of the time with pharmacological and nonpharmacological interventions. Effective treatment of anxiety, depression, and delirium necessitates a collaborative effort between the patient, family, and the health team. This chapter addresses the comprehensive patient-centered and family-focused care necessary for effective diagnosis, assessment, and treatment of anxiety, depression, and delirium in the palliative care patient.