The primary objectives in the treatment of schizophrenia are to reduce frequency and severity of psychotic exacerbation, ameliorate a broad range of symptoms, prevent relapses, and improve functional capacity and quality of life. Treatment includes medication and a range of psychosocial interventions. Antipsychotics are the cornerstone of pharmacological treatment for schizophrenia. The twenty antipsychotics available in our country have traditionally been classified into two major groups: first-generation (conventional) agents (FGAs) and second-generation (atypical) agents (SGAs), although this dichotomization can be misleading. Whereas the efficacy of these antipsychotic agents in the treatment of schizophrenia is broadly similar (with the exception of clozapine’s greater efficacy in otherwise treatment-refractory patients), there are significant differences in their side-effect profiles. Optimal individualized pharmacological treatment of schizophrenia requires an understanding of the nature of schizophrenia (multiple pathological dimensions, remitting and relapsing course), knowledge about the similarities and differences between available antipsychotic treatments, and awareness of how to use these treatments most effectively (targeted, measurement-based, individualized). In this paper, recent advances in antipsychotic therapy are summarized and basic principles of the Florida Medicaid Drug Therapy Management Program for the treatment of schizophrenia are articulated.