Sepsis occurs when the immune system responds to a localised infection at a systemic level, thereby causing tissue damage and organ dysfunction. Statins have proven health benefits in many diseases involving vascular inflammation and injury. Recent animal data suggest that the administration of a statin before a sepsis-inducing insult reduces morbidity and improves survival. The immunomodulatory and anti-inflammatory effects of statins, collectively referred to as pleiotropic effects, lend biological plausibility to such findings. Limited human data hint at reduced mortality rates in bacteraemic patients, and a reduced risk of sepsis in patients with bacterial infections concurrently taking statins. These lines of evidence point to a potential new treatment and prevention modality for sepsis. The stage is set for randomised controlled clinical trials that will determine whether statins represent a safe and beneficial treatment in critically ill, septic patients and whether statins are effective at preventing sepsis in high-risk clinical settings.