In this issue of the journal, 2 case reports are presented that illustrate explicit influences of structural brain lesions on psychiatric symptoms. In both cases, the patients had preexisting, classically diagnosed psychiatric disorders—schizophrenia in the first case and bipolar I disorder in the second case. In the first case, a 61-year-old woman with chronic paranoid schizophrenia experienced a marked reduction in psychotic symptoms after bilateral frontal strokes. In the second case, a 60-year-old man who had experienced manic and depressive episodes since his 20s developed partial complex seizures after having repeated head trauma in his 40s, with subsequent onset of chronic personality changes associated with temporal lobe epilepsy that made his psychiatric treatment a greater challenge. The presentations in these 2 cases raise intriguing neuropsychiatric questions concerning the effects on regional brain activity of a variety of nonpharmacological psychiatric interventions (eg, stereotactic neurosurgical techniques, deep brain stimulation, electroconvulsive therapy, certain types of psychotherapy), and concerning possible physiological pathways shared by seizure kindling in epilepsy and recurrent episodes of bipolar disorder.