Certain clinical features, like changes in presentation, the presence of neurological signs, and a poor response to treatment, mandate an organic evaluation of psychiatric illnesses. In this case series, four cases with established mental illnesses who presented with psychiatric symptoms, on evaluation by neuroimaging, were found to have neurological disorders like neurocysticercosis, sub-arachnoid hemorrhage, sub-dural hemorrhage, and lacunar infarction. They were managed with a combination of medical and surgical treatment and psychotropics, and no relapse of symptoms was noted at follow-up. The formulation of clinical practice guidelines can be a way forward in holistic management for such patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Psychiatry.)