Drug discovery has been very slow in the field of serious mental illness treatment, especially for schizophrenia. This reflects a fundamental lack of clear biological targets for drug development. This is a challenge for basic science and for pharmaceutical companies. There is some hope that new large genetic studies (i.e., the All of Us Research Program) will shed light on the underlying biology, which could lead to new treatments. Clozapine remains the most effective and underutilized antipsychotic, though it has important side effects. In this way, clozapine represents new treatment option for the many who have not tried it. There are some new treatments in development for both medication and medical devices (e.g., repetitive transcranial magnetic stimulation) for depression.