Treatment resistance in schizophrenia creates a persistent public health problem and leads to repeated hospitalization. In search for a treatment for such patients, psychiatrists have co-prescribed multiple psychotropic medications simultaneously. Such practice is based mostly on clinical experience, rather than research derived evidence. Such combinations may not be fully “effective” if the cost, adverse effect profile and the potential for noncompliance by patients secondary to regimen complexity are considered. Is it really wise to try these various combinations of costly medicines in the mental health system, which is already struggling with its limited resources and funding worldwide? However, if mental health policy makers restrict reimbursement for such “unproven” combinations, patients might not receive the benefits of some of these combinations, which are showing some promise for the treatment of resistant schizophrenia.