Approximately 50% of patients diagnosed with cancer die because of progressive disease. Psychotropic drugs are frequently used for the management of physical and psychosocial symptoms in these patients. Thalidomide, cannabinoids and melatonin are emerging agents for the management of cachexia. Psychostimulants have a defined role in the management of opioid-induced sedation. Haloperidol, tricyclic anti-depressants and newer anti-depressants also have an established role in the management of neuropsychiatric symptoms such as delirium or depression. Cancer patients present unique challenges for successful psychotropic therapy including older age, malnutrition, autonomic failure, borderline cognition, opioid and psychotropic therapy. A practical clinical approach which defines a specific target symptom, an outcome latency period, expected side effects, and reviews possible drug interactions, and frequent monitoring is outlined. Continued research is needed to further define the role of psychotropics in the management of the different physical and psychosocial symptoms in advanced cancer patients.