From its epidemiology to biology and psychological adaptation, this overview will discuss the recognition, treatment and comprehensive management of clinical depression and related states of demoralization.  Cytochrome P450 drug interactions occur with Tamoxifen, Irinotecan and the SSRI antidepressants. Serotonin syndrome is potentially life-threatening.  Untreated depression is associated with poorer adherence to anticancer treatment, reduced survival, higher likelihood of smoking, obesity and reduced exercise, as well as poorer quality of life. Risk of suicide or desire for hastened death can follow. Psycho-oncology has much to offer in the management of depression, the aggressive treatment of which can sustain life and optimise its quality.