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Many patients with depression, anxiety disorders, and other psychiatric disorders are treated with combinations of psychodynamic psychotherapy and medication. Whether this is better than monotherapy is an empirical question that requires much more extensive research than is currently available. When medications were first introduced to treat psychiatric illnesses, some psychopharmacologists insisted that it heralded a new area of “biological psychiatry” that would ultimately render psychotherapy obsolete. Psychodynamic theorists and practitioners, on the other hand, argued that psychopharmacology offered only a superficial approach to treatment. Fortunately, these battles are now largely supplanted by the belief that whatever treatment offers the patient the best outcome should be employed, regardless of the therapist's theoretical outlook. This should motivate more extensive study of the value of combination treatment. So far, the few studies that have been done suggest that the combination of psychodynamic psychotherapy and medication may be superior for the treatment of mood and anxiety disorders, but most of these studies have small sample sizes and involve only short-term psychotherapy. An examination of the neuroscience of mood and anxiety disorders and of the mechanism of action of psychodynamic psychotherapy and of antidepressant medication suggests several routes by which the two treatment modalities could be synergistic: stimulation of hippocampal neurogenesis; epigenetic regulation of gene expression; dendritic remodeling; enhanced prefrontal cortical control of limbic system activity; and action at specific neurohormonal and neurotransmitter targets. The evidence for each of these mechanisms is reviewed with an eye toward potential experiments that might be relevant to them.