Prescribing of antipsychotic medications for patients with delirium remains controversial. Concerns exist that these vulnerable and frail patients may be prescribed antipsychotics inappropriately as a substitute for non-pharmacological approaches when identifiable causes are not found or they challenge ward processes. Moreover, recent evidence suggests that antipsychotics may cause more harm than good in the palliative care patient group with delirium. On the other hand, guidelines in the United Kingdom and the Netherlands support prescribing of antipsychotics in certain circumstances, and a large European survey has revealed that antipsychotics tend to be prescribed first line for hyperactive delirium. Never before, therefore, is there a greater need to examine whether indeed these medications are clinically useful for the treatment of delirium. With this in mind, evidence-based arguments for and against prescribing antipsychotics for the treatment of delirium are presented in this debate article. The paper concludes with a moderation piece to help guide clinical practice.