Antipsychotics have numerous evidence-based uses in the twenty-first century, including schizophrenia spectrum and other psychotic disorders, bipolar disorder, unipolar major depression, behavioral disturbances of autism, tic disorders, and obsessive compulsive disorder [1]. The application of antipsychotic therapy in many of these conditions is adjunctive, and it may be withdrawn during less active phases of the illness. For patients with schizophrenia spectrum disorders, antipsychotics are the foundation of treatment without which the patient is at risk for relapse, and the attendant psychiatric, social, and legal consequences [2, 3]. Given the level of disability often encountered with the onset of illness, the care and management of individuals with schizophrenia exerts a significant economic toll on society [4–6]; moreover, this burden accrues most directly to families and direct caregivers in the form of financial loss compounded by stress and decreased quality of life [7, 8]. Of particular concern are the disproportionate direct and indirect costs associated with treatment-resistant schizophrenia (TRS) [4] (see Figure 0.1).