Delirium has been recognised in the medical literature since antiquity and is particularly common in mechanically ventilated intensive care patients. Given the sheer number of potential precipitating and predisposing factors that can contribute to the development of delirium, predicting and preventing delirium remain challenging. However, as it is associated with a variety of adverse outcomes, including increased mortality and dependence, as well as increased costs, reliable delirium prevention remains the goal. Dexmedetomidine is the agent with the strongest evidence of both a preventative and a therapeutic effect. The benefit of multicomponent non-pharmacological interventions has not been demonstrated to improve outcomes in randomised controlled trials, but is associated with a reduction in delirium occurrence and severity in the observational data. Future studies should address novel preventative and therapeutic interventions and examine evidence of benefit across motoric subtypes, as well as seek to understand data-driven classifications of delirium. With modern technology and design, as well as more effective therapeutics and an integrated multimodal approach to prevention, a future in the intensive care unit (ICU) without delirium may be possible.