Chronic pain is among the most common conditions to initiate medical care; 40% of patients victimized by chronic pain are not under the supervision of a physician, and about 70% of patients with severe pain are receiving pain medical care. About dollar 100 billion is an annual estimated cost representing loss of productivity, increased medical costs, and income loss. Major depressive disorder is not infrequently encountered in daily clinical practice often presenting with somatic complaints that include varieties of pain, and these may be so prominent as to direct the treatment to the somatic complaint evaluation to the exclusion of underlying psychopathology. Anxiety disorders and other psychiatric disorders may also present with such a somatization evaluation focus. Serotonin noradrenergic reuptake inhibitors (SNRIs), ie, venlafaxine and duloxetine, offer benefits over tricyclic antidepressants and serotonin reuptake inhibitors. Years of experience with venlafaxine representing a first-line pharmacotherapy for depression and anxiety have benefited patients presenting with somatic symptoms with a robust onset. A more rapid achievement by venlafaxine of remission and a high-quality pharmacokinetic and pharmacodynamic profile lead to patient compliance and facilitate both fewer relapses and recurrences. Duloxetine is broadly discussed, revealing pharmacokinetic, pharmacodynamic, adverse/side effects, cautions with requisite patient-specific selection, and laboratory monitoring. The management of somatic pain complaints of physical and psychiatric origin is discussed.