Aim: The aim of this paper is to determine the efficacy, advantages, and disadvantages of using antipsychotics in polytherapy in relation to monotherapy and to look at the importance of the role pharmacists, as the most accessible healthcare professionals, can play in treating schizophrenia and antipsychotics. Subjects and method: For the purposes of this research, a systematic and retrospective review of scientific and professional literature was made. Currently valid therapeutic guidelines, publications of professional associations and institutions, the drug database of the Agency for Medicinal Products and Medical Devices and other available sources were researched. Results: The most common combinations of antipsychotics were identified and separated into those that include clozapine and those that do not. The advantages and disadvantages of each combination were highlighted. The importance of involving public pharmacists was emphasized. Conclusion: Polytherapy is the only viable solution if all other therapy attempts have consistently proven inadequate, however, in clinical practice polytherapy is still introduced much earlier despite the recommendations of all leading guidelines. Due to insufficient quality of randomized studies, preference should be given to monotherapy treatment. If preference is in fact given to polytherapy, the patient should be closely monitored so that the benefits of the combination outweigh the risk of additional side effects and increased treatment costs. Public pharmacists can play a major role in improving adherence, and it is exactly non-adherence that is one of the most common problems in the treatment of schizophrenia. Currently, the role of public pharmacists is underutilized and additional training and engagement of the profession is needed to make changes that will benefit an overburdened health system.