Pain is accompanied by an emotional response. It produces emotions such as irritability, fear, sadness, helplessness or despair, and chronic pain produces them in more disabling intensity. Doctors always recognize these emotional responses and take steps to relieve them, such as empathizing, showing concern, giving encouragement, or even a gentle hand on the shoulder. Pain is a symptom of a variety of psychiatric illnesses namely affective disorder, somatoform disorder, factitious disorder, malingering and psychosis. Amitriptyline, duloxetine and mirtazapine are the commonly used psychotropic drugs by pain specialists. Some of the additional information about drugs such as selective serotonin reuptake inhibitors, monoamine oxidase inhibitors and serotonin-norepinephrine reuptake inhibitors are discussed in this chapter.