Background: Clozapine, a tricyclic dibenzodiazepine, is an atypical antipsychotic drug. It has the best effect among all antipsychotic drugs and has a strong antagonistic activity on D4-dopaminergic receptors, serotonergic, noradrenergic, histamine and cholinergic M2 receptors. Clozapine is uniquely effective and the only licensed agent for treatment-resistant schizophrenia. It reduces symptoms of psychosis by 40%, It significantly decreases psychiatric-related hospital admissions and mortality. However, clozapine is associated with agranulocytosis, metabolic side effects like insulin resistance with increased risk of type II diabetes and a variety of cardiovascular problems, including myocarditis. Aim: The current review provides the evaluation of clozapine, outlining its pharmacological properties, clinical applications, mechanism of action as well as its toxic effects and management. Conclusion: In summary, researchers have frequently emphasized the significance of clozapine therapy as the cornerstone of the treatment of psychosis.