SPICE III evaluated whether dexmedetomidine should be used as the sole or primary sedative early in mechanically ventilated ICU patients compared with usual care using other sedatives. More than 4,000 patients were randomised, making the trial one of the largest modern evaluations of ICU sedation. Ninety-day mortality was similar between the two groups. Many patients receiving dexmedetomidine still required additional propofol or midazolam to achieve the targeted light level of sedation, and bradycardia and hypotension were more common. The study therefore challenged the idea that choosing dexmedetomidine as the default early sedative would, by itself, improve survival. The broader clinical lesson is that sedation quality depends on the whole strategy—depth of sedation, daily reassessment, analgesia, delirium prevention and liberation from ventilation—not simply on which drug is used. Dexmedetomidine may still have a valuable role when light, cooperative sedation is desired, particularly in patients who need to be interactive during weaning or assessment. But the trial does not support routine replacement of all other sedatives with dexmedetomidine. For intensivists, SPICE III reinforces a patient-centred approach in which the sedation target and clinical goals are defined first, followed by selection and titration of the agent that best fits that patient.