This article looks at the challenges of sedoanalgesia for sepsis patients, and argues for a personalised approach. Sedation is a necessary part of treatment for patients in intensive care to reduce stress and anxiety and improve long-term prognoses. Sepsis patients present particular difficulties as they are at increased risk of a wide range of complications, such as multiple organ failure, neurological dysfunction, septic shock, ARDS, abdominal compartment syndrome, vasoplegic syndrome, and myocardial dysfunction. The development of any one of these complications can cause the patient’s rapid deterioration, and each has distinct implications in terms of appropriate and safe forms of sedation. In this way, the present article reviews the sedative and analgesic drugs commonly used in the ICU and, placing special emphasis on their strategic administration in sepsis patients, develops a set of proposals for sedoanalgesia aimed at improving outcomes for this group of patients. These proposals represent a move away from simplistic approaches like avoiding benzodiazepines to more “objective-guided sedation” that accounts for a patient’s principal pathology, as well as any comorbidities, and takes full advantage of the therapeutic arsenal currently available to achieve personalised, patient-centred treatment goals.