People with schizophrenia die prematurely from comorbid physical diseases, particularly from cardiometabolic disturbances. Although some host vulnerability exists, there is also mounting evidence of a relationship between metabolic disturbances and antipsychotic medications. Clinicians must now make a careful appraisal of these risks when choosing an antipsychotic drug. Additionally, clinicians are required to undertake close monitoring for metabolic disturbances during antipsychotic therapy. Although switching antipsychotic medications is currently the preferred strategy if metabolic disturbances occur, there are other pharmacologic and nonpharmacologic approaches that might also prove beneficial for the individual patient. Metabolic disturbance and the detection and management thereof currently hold "center stage" in the psychopharmacology of schizophrenia.