Maintenance of response in schizophrenia is largely dependent on compliance with antipsychotic treatment. When people with schizophrenia are responsible for their own treatment, partial or non-adherence is common and usually results in relapse. Assured compliance with antipsychotic treatment is possible when long-acting injectable antipsychotics are given by healthcare staff, but some patients may not consent to treatment for a variety of reasons. An alternative to long-acting injections is the use of supervised oral administration of long-acting antipsychotics. This method assures compliance with prescribed regimens without the need for injections. To be suitable for once-weekly administration as an oral formulation, an antipsychotic needs to have a sufficiently long duration of action and to be well tolerated in high doses. There is evidence that weekly oral administration of either pimozide or penfluridol is effective and well tolerated in the treatment of schizophrenia. Other drugs potentially suitable for once-weekly oral administration include aripiprazole, brexpiprazole and cariprazine.