OBJECTIVE Delirium is a very common and serious disorder with high morbidity and mortality. Despite symptomatic treatment the outcome can be poor for some especially when no underlying cause is identified. As a result, various strategies for delirium prevention have been assessed. Pharmacological agents such as antipsychotics, acetylcholinesterase inhibitors, sleep-wake cycle regulators, anti-inflammatories and others have been advocated for a potential role in delirium prevention. The aim of this paper is to review the available evidence for their use in the prevention of delirium. METHODS An electronic search was carried out using Medline, EMBASE and Cochrane for randomised controlled trials (RCTs) and other studies. The words delirium, prevention, intervention, pharmacological, prophylactic, antipsychotics, acetylcholinesterase inhibitors, sleep and anti-inflammatories were used. References from selected papers were also searched. RESULTS No multi-centre RCT has been identified. Few trials and other studies have been published so far assessing the prophylactic role of antipsychotics, acetylcholinesterase inhibitors, hypnotics, melatonin, and gabapentin. As these studies tested different drugs, regimes and protocols in diverse populations no meaningful comparison can be made. CONCLUSION To date there is conflicting and inconsistent data regarding the efficacy of pharmacological treatment for delirium prevention. Positive reports in few of the studies justify further assessment of the potential for some pharmacological agents in the prevention of delirium. Well designed and appropriately powered RCTs are now needed. However, based on available evidence so far, no recommendation can be made to justify the routine clinical prophylactic use of any pharmacological agent in the prevention of delirium.