Catatonic syndrome is frequently observed over the course of severe mental disorders and general medical conditions, but when catatonia occurs in psychiatric patients with co-morbid medical or neurologic conditions, diagnosis and management may be challenging. Several medical conditions may cause catatonia in psychiatric patients, but some, such as brain injury, infections, hyponatremia and critical illness, may be most relevant in this population. Alongside appropriate etiologic treatment, benzodiazepines and electroconvulsive therapy in refractory cases are effective and safe, and may resolve catatonic syndrome rapidly. When newly-onset psychotic symptoms in catatonic patients with established psychotic disorders occur, delirium should be suspected and appropriately managed. An extensive clinical and laboratory diagnostic workup to determine the underlying etiology of catatonic syndrome should be carried out. In cases of acute multi-morbidity, the exact cause of catatonic syndrome in psychiatric patients may be unclear. It is recommended to avoid antipsychotic drugs in acutely catatonic patients, because they may exacerbate the catatonic symptoms. The akinetic type of catatonia should be differentiated from hypoactive delirium, as treatments for these syndromes differ substantially. When a psychiatric patient presents with symptomatology of both catatonia and delirium, treatment is particularly challenging.