HMG-CoA reductase inhibitors, or statins, are among the most commonly prescribed pharmaceuticals in the world, especially among the elderly. The remarkable conjuncture of this fact with the rising incidence of severe sepsis among people over age 65 could prove to be of serendipitous benefit, because numerous actions of the statins make them of potential use in the prevention and treatment of severe sepsis. Severe sepsis continues to be a highly lethal condition, for which there are, as yet, no effective pharmacological treatments, save antibiotics. We explore the biological plausibility of statins as prophylaxis agents and as treatment for severe sepsis and thoroughly review the preclinical and clinical studies that have explored the effects of statins in infected and septic patients. Statins remain only promising treatments for severe sepsis, without convincing evidence that they reduce patient mortality. Ongoing randomized trials may provide conclusive evidence, whether positive or negative.