Treatment-resistant schizophrenia (TRS) poses a significant therapeutic challenge in psychiatric practice. Clozapine is recognized as a treatment of choice in TRS but is not always effective in alleviating patients' symptoms. Additionally, clozapine therapy is associated with multiple side effects and monitoring requirements that often limit its use and negatively affect patients' compliance with the treatment. Although clozapine augmentation options are available, there is currently no alternative monotherapy proven to be effective in TRS. We present a case of a young man with TRS who failed to respond to appropriate trials of risperidone, aripiprazole and also clozapine, and who experienced impairing adverse effects of clozapine that made further clozapine treatment not only futile but also detrimental to his health. He was successfully treated with cariprazine monotherapy, which culminated in the remission of his both positive and negative symptoms of psychosis as well as in the marked improvement in social functioning. Cariprazine, a newer atypical antipsychotic endowed with a D3-preferring mode of action, may offer a better tolerated and more acceptable treatment option for patients with difficult-to-treat psychotic symptoms.