Schizophrenia is a psychiatric disorder that causes severe cognitive, behavioral and social dysfunction, responsible for a shortening of the life expectancy of patients, with an increased risk of suicide, cardiovascular disease and cancer. The management of patient with schizophrenia is global and atypical antipsychotics, antagonizing dopamine pathway, are the first line pharmacological treatment. Clozapine, the first atypical antipsychotic discovered, is currently still the most effective molecule against schizophrenia, while causing less extrapyramidal side effects. Its particular pharmacological behavior towards serotonergic, muscarinic and NMDA receptors, seems essential to its action. However, clozapine is responsible for immunological and metabolic lethal adverse events, preventing its wider use. Clozapine is therefore reserved for resistant schizophrenia cases. Monitoring patients with different scales such as the Brief Psychiatric Rating Scale and the Positive And Negative Syndrome Scale showed that there were forms of ultra-resistant schizophrenia. The treatment in this case, must be customized to the patient's symptomatology, but the combination of clozapine with other pharmacological or non-pharmacological treatments, shows yet only small improvements.