Antipsychotic monotherapy (APM) is considered best-acceptable treatment option regardless of antipsychotic class and formulation types for treating schizophrenia. However, antipsychoticpolypharmacy (APP) has been also widely utilized in routine clinical practice. Despite APP has some clinical benefits it has also numerous pitfalls in relation with increased total number and doses of APs leading to adverse events as well as decrease of treatment adherence and persistence resulting in poor clinical outcomes. Recent introduction of long-acting injectableantipsychotics (LAIs) to the market has offered a chance for better medication adherence/persistence and also provided a simplification of treatment regime leading to more stabilized treatment for schizophreniapatients. When we cannot stay away from APP in the treatment of schizophrenia, clinicians need to find more proper APP regimens and thereby utilization of APP in efficient way should be a practical strategy to benefit schizophreniapatient in a real world treatment setting. With this regard, LAIs can be one of available APP regimen for treatment of schizophrenia in routine practice since their clinical utility and pharmacokinetic stability over oral APs have been well-elaborated today. However, when we have to commence LAIs as a part of APP with oral APs or other LAIs, every effort should be made before doing so whether or not validated and available treatment options or other clinical factors were not done or evaluated yet. Any treatment guidelines do not support APP regardless of the formulation of APP regimen or address two or more LAIs for treatment of schizophrenia till today.