The currently available antipsychotics mostly treat the positive symptoms of schizophrenia and have at least one adverse effect as a potential liability. Encouraging data suggest potential efficacy for a variety of new agents for the treatment of total symptoms and/or specific symptom domains of schizophrenia. Mechanisms of action that are under investigation include dopamine D3 antagonism/serotonin 5-HT1A partial agonism; combined dopamine, serotonin, and glutamate modulation; phosphodiesterase 10A inhibition; trace amine-associated receptor-1 (TAAR1) agonism plus 5-HT1A agonism; 5-HT2A inverse agonism; sigma-2/5-HT2A antagonism; D-amino acid oxidase (DAAO) inhibition; glycine transporter-1 inhibition; vesicular monoamine transporter-2 antagonism; mu opioid antagonism added to olanzapine; and novel long-acting injectable antipsychotic formulations. It is hoped that ongoing and recently completed trials for agents with known and/or novel mechanisms of action will lead to approved treatments that effectively target the various symptom domains of schizophrenia, minimize the risk for a broad range of clinically relevant adverse effects, and improve functional outcomes for patients. Some novel treatments have already received approval for use in patients with schizophrenia. This brief report discusses recently approved novel agents and potential new treatment options for schizophrenia that are being investigated.