Polypharmacy is usually employed where single drugs are considered insufficiently effective. Some polypharmacy is rational and evidence based, some neither. Antipsychotic polypharmacy remains stubbornly widespread despite condemnation of the practice by numerous bodies. The practice could not be said to be evidence based. Its persistence probably stems from a well-meaning desire to improve response and from confusion about the mechanism of action of antipsychotics. In particular, the concept that more antipsychotic(s) must always be, or might be, ‘better’ is virtually groundless. Nonetheless, some specific antipsychotic polypharmacy regimens have shown particular benefits on adverse effect profiles. Targeted, evidence-based polypharmacy may be the way forward.