Depression is an illness that causes symptoms in both the body and the brain, i.e., painful physical as well as emotional and vegetative symptoms. Ascending serotonergic and noradrenergic pathways may mediate the emotional and vegetative symptoms of depression and can potentially be targets of serotonin and norepinephrine reuptake inhibitors to obtain relief of these symptoms. Descending serotonergic and noradrenergic pathways may regulate the painful physical symptoms of depression, and when targeted by serotonin and norepinephrine reuptake inhibitors, relieve these symptoms as well. Selective serotonin reuptake inhibitors have a remission rate of 35%, and dual-action reuptake inhibitors have a 45% remission rate. Despite these results, the best treatment of depression currently recognizes the 3 types of symptoms and targets them all for complete remission no matter which drug is used.