Dr. Meltzer directs a multifaceted research program in schizophrenia and bipolar disorder which is devoted to developing more effective treatments. He is one of a few clinical researchers also heavily engaged in basic research. He is particularly renowned for having been the principal investigator of the seminal trials that led to the approval of clozapine for treatment-resistant schizophrenia (1988) and patients who are at high risk for suicide (2003). He also is credited with articulating the theory that atypical antipsychotics such as clozapine owe much of their advantage over typical drugs to the balance between serotonin and dopamine receptor blockade (1989). Dr. Meltzer is an active clinician who directs the clinical trial research effort at mental health centers in Chicago and Cleveland.

Prior to joining Northwestern, Dr. Meltzer taught at Vanderbilt University, where he also directed the psychosis program.