Clozapine is an atypical antipsychotic which is considered a gold standard in treatment for treatment-resistant schizophrenia. This drug is acting on multiple receptors like dopaminergic receptors, serotonergic receptors, adrenergic receptors, and muscarinic receptors. The action on dopaminergic and serotonergic receptors alleviates the positive and negative symptoms of schizophrenia but action on some other receptors explains its side effects. Though it is an outstanding drug in treatment-resistant schizophrenia, treatment-resistant mood disorder, co-morbid use of alcohol and other substances in schizophrenia, hostility, and suicidality of the patient with schizophrenia, due to its severe side effects among which some are fatal, it is of having limited use. Before starting the therapy, a proper history should be taken, a thorough physical examination and a review of the investigation to be done to get the baseline of the specific patient. During the therapy, the patient should be frequently checked for changes in different parameters like vital signs, absolute neutrophil counts, BMI, biological functions, etc by using a clozapine assessment checklist. A proper assessment will help to prevent the worsening of the side effects. If any adverse effect is observed, then symptomatic management is required.