The use of several drugs is quite common in the treatment of diseases, such as hypertension and epilepsy. Since the 1990s, there has been a tendency to use simultaneously two or more antipsychotic drugs to treat schizophrenia patients. It is estimated that 30–40% of patients are treated with two or more antipsychotic drugs. This was also confirmed by research carried out in Poland. This is despite the fact that the standards of pharmacological treatment of schizophrenia consistently recommend the use of monotherapy. There are also doubts about the safety of polytherapy. So far, it has not been clearly shown whether this is more effective than monotherapy. A recently published meta-analysis showed that only the combined use of clozapine and aripiprazole is more effective than other monotherapy and polytherapy. It has not yet been confirmed that the combined use of two antipsychotic drugs was associated with a higher risk of metabolic syndrome symptoms and QTc segment prolongation. The paper presents data on the scale of the phenomenon of polytherapy as well as publications on the effectiveness and safety of such proceedings as compared to monotherapy. Due to the ambiguity of the results, it is difficult to make clear recommendations regarding the management of monotherapy ineffectiveness. The work ends with a few questions that concern doubts about how to treat patients with schizophrenia to make the treatment rational.