The global COVID-19 pandemic has disrupted every aspect of the healthcare system. Apart from the issues surrounding COVID-19 itself, care for existing patients has met many challenges. One such challenge is caring for patients who are on clozapine treatment and have been confirmed positive for COVID-19. Schizophrenia has been considered to have a deep connection with the immune system, and clozapine can induce further changes in this system. COVID-19 can ravage the compromised immune system and aggravate tissue damage. The intricate relations between schizophrenia, clozapine, and COVID-19 make it difficult to predict the clinical course of COVID-19 in clozapine-treated patients. However, the rigid prohibition on using clozapine if COVID-19 is confirmed may harm patients. Patients who have to use clozapine are often refractory cases with no alternatives. Therefore, the decision to maintain or stop clozapine must be made after a comprehensive review of the patient's unique situation. To do this, theoretical and practical issues surrounding the use of clozapine in COVID-19 should be reviewed and discussed. In this review, we gather useful information surrounding this issue and present an overview. Focusing on the immune system, various theoretical possibilities that could arise from schizophrenia, clozapine, and COVID-19 were carefully examined, and practical checklists for the care of these patients were explored. It is hoped that this review will convince many clinicians to pay attention to this momentous issue and facilitate more active sharing of clinical experiences.