The term distress has been used in screening and triage of patients with psychosocial concerns in a variety of care settings in the past decade and is becoming the screening term of choice in many cancer centers and clinics. Although a distress scale represents a one-dimensional assessment of the patient, the causes of distress in cancer are multi-dimensional. Antidepressant medication therapy is considered appropriate treatment for depressive disorders co-occurrent with cancer, although only a small number of trials are sufficiently rigorous, given high dropout rates and limited information about adverse drug reactions. Psychotherapy is helpful for cancer patients with depression and distress. Screening caregivers for depression and distress can be a very important psychosocial intervention, both for the caregiver and for the cancer patient. In patients with a history of cancer, the consultation psychiatrist must be mindful of personal trauma and medical consequences associated with that experience.