The review is devoted to comparative analysis of antipsychotics of three generations. When writing the review, a systematic search in the databases PubMed, Medline, Elsevier was carried out, a simple filter for keywords was used. Pharmacological and clinical issues of antipsychotic therapy were considered, the mechanisms of action of antipsychotics of different generations were revealed. Current trends in the development of approaches to the therapy of schizophrenia and the concept of “atypicality” of antipsychotics were discussed. A comparative analysis of indications for use, tolerance (safety of use) and efficacy of various antipsychotic drugs with an emphasis on the effect on negative (primary, persistent) symptoms has been conducted. The hypothesis underlying new approaches to the therapy of schizophrenia, based on the effect on dopamine autoreceptors, consisting of a high density of D2 and low density of D3 receptors, has been presented. It has been shown that antipsychotics of the third generation open up new possibilities in the therapy of psychosis within the framework of a personalized approach in psychiatry with the achievement of functional recovery of patients. The characteristics of the drugs - representatives of the third generation of antipsychotics - aripiprazole and cariprazine were given. The uniqueness of cariprazine as the only drug that inhibits D3 receptors in vitro, as well as in vivo in patients with schizophrenia was emphasized. The data of evidence-based studies of the effectiveness of cariprazine in the treatment of negative, including predominant negative symptoms were presented.