Schizophrenia is a psychiatric disease which affects one percent of population. It is most common in young adults. It is primarily treated with typical and atypical antipsychotics. Resistant schizophrenia is a condition diagnosed after no response is noticed to two different antipsychotics of which one is atypical. The treatment has to be undertaken with adequate doses and duration of therapy. Clozapine is the golden standard in the treatment of therapy-resistant schizophrenia. It has shown its superiority among other antipsychotics in various studies. Aside from greater effectiveness, advantages include absence of extrapyramidal side effects. During clozapine treatment, regular blood tests should be performed as a screening method for agranulocytosis. Twenty to thirty percent od schizophrenia patients suffer from treatment resistant schizophrenia. Sixty percent of the latter ones show no therapeutic response to clozapine. In conclusion twelve to eighteen percent of all patients suffering from schizophrenia show no response to any form of treatment. Attempts to augment clozapine effectiveness are being made by increasing the dose of monotherapy, using antipsychotic polipharmacy or adding other types of drugs to clozapine. Unfortunately, these augmentation methods have not yet proven themselves to be effective enough to be added to standard therapy algorythms. On the other hand, electroconvulsive therapy is neuromodulatory method that shows promise in increasing therapeutic success. Although many methods of treatment are being researched, therapy-resistant schizophrenia remains a clinical challenge which affects a significant percentage of population and will require additional research.